The cell is the basic structural and biological unit of all known living organisms. A cell is the smallest unit of life. Cells are called the "building blocks of life"; the study of cells is called cellular biology. Cells consist of cytoplasm enclosed within a membrane, which contains many biomolecules such as proteins and nucleic acids. Organisms can be classified as multicellular; the number of cells in plants and animals varies from species to species, it has been estimated that humans contain somewhere around 40 trillion cells. Most plant and animal cells are visible only under a microscope, with dimensions between 1 and 100 micrometres. Cells were discovered by Robert Hooke in 1665, who named them for their resemblance to cells inhabited by Christian monks in a monastery. Cell theory, first developed in 1839 by Matthias Jakob Schleiden and Theodor Schwann, states that all organisms are composed of one or more cells, that cells are the fundamental unit of structure and function in all living organisms, that all cells come from pre-existing cells.
Cells emerged on Earth at least 3.5 billion years ago. Cells are of two types: eukaryotic, which contain a nucleus, prokaryotic, which do not. Prokaryotes are single-celled organisms, while eukaryotes can be either single-celled or multicellular. Prokaryotes include two of the three domains of life. Prokaryotic cells were the first form of life on Earth, characterised by having vital biological processes including cell signaling, they are simpler and smaller than eukaryotic cells, lack membrane-bound organelles such as a nucleus. The DNA of a prokaryotic cell consists of a single chromosome, in direct contact with the cytoplasm; the nuclear region in the cytoplasm is called the nucleoid. Most prokaryotes are the smallest of all organisms ranging from 0.5 to 2.0 µm in diameter. A prokaryotic cell has three architectural regions: Enclosing the cell is the cell envelope – consisting of a plasma membrane covered by a cell wall which, for some bacteria, may be further covered by a third layer called a capsule.
Though most prokaryotes have both a cell membrane and a cell wall, there are exceptions such as Mycoplasma and Thermoplasma which only possess the cell membrane layer. The envelope gives rigidity to the cell and separates the interior of the cell from its environment, serving as a protective filter; the cell wall consists of peptidoglycan in bacteria, acts as an additional barrier against exterior forces. It prevents the cell from expanding and bursting from osmotic pressure due to a hypotonic environment; some eukaryotic cells have a cell wall. Inside the cell is the cytoplasmic region that contains the genome and various sorts of inclusions; the genetic material is found in the cytoplasm. Prokaryotes can carry extrachromosomal DNA elements called plasmids, which are circular. Linear bacterial plasmids have been identified in several species of spirochete bacteria, including members of the genus Borrelia notably Borrelia burgdorferi, which causes Lyme disease. Though not forming a nucleus, the DNA is condensed in a nucleoid.
Plasmids encode additional genes, such as antibiotic resistance genes. On the outside and pili project from the cell's surface; these are structures made of proteins that facilitate communication between cells. Plants, fungi, slime moulds and algae are all eukaryotic; these cells are about fifteen times wider than a typical prokaryote and can be as much as a thousand times greater in volume. The main distinguishing feature of eukaryotes as compared to prokaryotes is compartmentalization: the presence of membrane-bound organelles in which specific activities take place. Most important among these is a cell nucleus, an organelle that houses the cell's DNA; this nucleus gives the eukaryote its name, which means "true kernel". Other differences include: The plasma membrane resembles that of prokaryotes in function, with minor differences in the setup. Cell walls may not be present; the eukaryotic DNA is organized in one or more linear molecules, called chromosomes, which are associated with histone proteins.
All chromosomal DNA is stored in the cell nucleus, separated from the cytoplasm by a membrane. Some eukaryotic organelles such as mitochondria contain some DNA. Many eukaryotic cells are ciliated with primary cilia. Primary cilia play important roles in chemosensation and thermosensation. Cilia may thus be "viewed as a sensory cellular antennae that coordinates a large number of cellular signaling pathways, sometimes coupling the signaling to ciliary motility or alternatively to cell division and differentiation." Motile eukaryotes can move using motile flagella. Motile cells are absent in flowering plants. Eukaryotic flagella are more complex than those of prokaryotes. All cells, whether prokaryotic or eukaryotic, have a membrane that envelops the cell, regulates what moves in and out, maintains the electric potential of the cell. Inside the membrane, the cytoplasm takes up most of the cell's volume. All cells possess DNA, the hereditary material of genes, RNA, containing the information necessary to build various proteins such as enzymes, the cell's primary machinery.
There are other kinds of biomolecules in cells. This article lists these primary cellular components briefly
The lymphatic vessels are thin-walled vessels structured like blood vessels, that carry lymph. As part of the lymphatic system, lymph vessels are complementary to the cardiovascular system. Lymph vessels are lined by endothelial cells, have a thin layer of smooth muscle, adventitia that bind the lymph vessels to the surrounding tissue. Lymph vessels are devoted to the propulsion of the lymph from the lymph capillaries, which are concerned with absorption of interstitial fluid from the tissues. Lymph capillaries are larger than their counterpart capillaries of the vascular system. Lymph vessels that carry lymph to a lymph node are called afferent lymph vessels, those that carry it from a lymph node are called efferent lymph vessels, from where the lymph may travel to another lymph node, may be returned to a vein, or may travel to a larger lymph duct. Lymph ducts drain the lymph into one of the subclavian veins and thus return it to general circulation. Lymph flows away from the tissues to lymph nodes and to either the right lymphatic duct or the largest lymph vessel in the body, the thoracic duct.
These vessels left subclavian veins respectively. The general structure of lymphatics is based on that of blood vessels. There is an inner lining of single flattened epithelial cells composed of a type of epithelium, called endothelium, the cells are called endothelial cells; this layer functions to mechanically transport fluid and since the basement membrane on which it rests is discontinuous. The next layer is that of smooth muscles that are arranged in a circular fashion around the endothelium, which by shortening or relaxing alter the diameter of the lumen; the outermost layer is the adventitia. The general structure described here is seen only in larger lymphatics; the smallest vessels lack both the outer adventitia. As they proceed forward and in their course are joined by other capillaries, they grow larger and first take on an adventitia, smooth muscles; the lymphatic conducting system broadly consists of two types of channels—the initial lymphatics, the prelymphatics or lymph capillaries that specialize in collection of the lymph from the ISF, the larger lymph vessels that propel the lymph forward.
Unlike the cardiovascular system, the lymphatic system has no central pump. Lymph movement occurs despite low pressure due to peristalsis and compression during contraction of adjacent skeletal muscle and arterial pulsation; the lymphatic circulation begins with blind ending permeable superficial lymph capillaries, formed by endothelial cells with button-like junctions between them that allow fluid to pass through them when the interstitial pressure is sufficiently high. These button-like junctions consist of protein filaments like platelet endothelial cell adhesion molecule-1, or PECAM-1. A valve system in place here prevents the absorbed lymph from leaking back into the ISF. There is another system of semilunar valves that prevents back-flow of lymph along the lumen of the vessel. Lymph capillaries have many interconnections between them and form a fine network. Rhythmic contraction of the vessel walls through movements may help draw fluid into the smallest lymphatic vessels, capillaries. If tissue fluid builds up the tissue will swell.
As the circular path through the body's system continues, the fluid is transported to progressively larger lymphatic vessels culminating in the right lymphatic duct and the thoracic duct. The system collaborates with white blood cells in lymph nodes to protect the body from being infected by cancer cells, viruses or bacteria; this is known as a secondary circulatory system. The lymph capillaries drain the lymph to larger contractile lymphatics, which have valves as well as smooth muscle walls; these are called the collecting lymphatics. As the collecting lymph vessel accumulates lymph from more and more lymph capillaries in its course, it becomes larger and is called the afferent lymph vessel as it enters a lymph node. Here the lymph is removed by the efferent lymph vessel. An efferent lymph vessel may directly drain into one of the lymph ducts, or may empty into another lymph node as its afferent lymph vessel. Both the lymph ducts return the lymph to the blood stream by emptying into the subclavian veins The functional unit of a lymph vessel is known as a lymphangion, the segment between two valves.
Since it is contractile, depending upon the ratio of its length to its radius, it can act either like a contractile chamber propelling the fluid ahead, or as a resistance vessel tending to stop the lymph in its place. Lymph vessels act as reservoirs for plasma and other substances including cells that have leaked from the vascular system and transport lymph fluid back from the tissues to the circulatory system. Without functioning lymph vessels, lymph cannot be drained and edema results; the afferent lymph vessels enter at all parts of the periphery of the lymph node, after branching and forming a dense plexus in the substance of the capsule, open into the lymph sinuses of the cortical part. It carries unfiltered lymph into the node. In doing this th
Receptor-mediated endocytosis called clathrin-mediated endocytosis, is a process by which cells absorb metabolites, proteins – and in some cases viruses – by the inward budding of the plasma membrane. This process forms vesicles containing the absorbed substances and is mediated by receptors on the surface of the cell. Only the receptor-specific substances can enter the cell through this process. Although receptors and their ligands can be brought into the cell through a few mechanisms, clathrin-mediated endocytosis remains the best studied. Clathrin-mediated endocytosis of many receptor types begins with the cargo ligands in the luminal compartment of the cell binding to receptors on the cell membrane; the cargo ligand and receptor will recruit adaptor proteins and clathrin triskelions to the outside membrane of the cell around where budding will form. Budding of the plasma membrane occurs, forming a clathrin coated pit. Other receptors can nucleate a clathrin-coated pit allowing formation around the receptor.
A mature pit will be cleaved from the plasma membrane through the use of membrane binding and fission proteins such as dynamin, forming a clathrin-coated vesicle that uncoats and fuses to a sorting endosome. Once fused, the endocytosed cargo can be sorted to lysosomal, recycling, or other trafficking pathways; the function of receptor-mediated endocytosis is diverse. It is used for the specific uptake of certain substances required by the cell; the role of receptor-mediated endocytosis is well recognized up take downregulation of transmembrane signal transduction but can promote sustained signal transduction. The activated receptor becomes internalised and is transported to late endosomes and lysosomes for degradation. However, receptor-mediated endocytosis is actively implicated in transducing signals from the cell periphery to the nucleus; this became apparent when it was found that the association and formation of specific signaling complexes is required for the effective signaling of hormones.
Additionally it has been proposed that the directed transport of active signaling complexes to the nucleus might be required to enable signaling as random diffusion is too slow and mechanisms permanently downregulating incoming signals are strong enough to shut down signaling without additional signal-transducing mechanisms. Using fluorescent dyes to tag specific molecules in living cells, it is possible to follow the internalization of cargo molecules and the evolution of a clathrin-coated pit by fluorescence microscopy. Since the process is non-specific, the ligand can be a carrier for larger molecules. If the target cell has a known specific pinocytotic receptor, drugs can be attached and will be internalized. To achieve internalisation of nanoparticles into cells, such as T cells, antibodies can be used to target the nanoparticles to specific receptors on the cell surface; this is one method of improving drug delivery to immune cells. Induction within minutes of exposure to excess ligand.
The formation of these vesicles is sensitive to inhibition by wortmannin The initiation of vesicle formation can be delayed/inhibited by temperature variations Non-specific, adsorptive pinocytosis Pinocytosis Phagocytosis Viropexis Bulk endocytosis Endocytosis CytoChemistry.net- A lecture on RME with some nice pictures
Pattern recognition receptor
Pattern recognition receptors play a crucial role in the proper function of the innate immune system. PRRs are germline-encoded host sensors, they are proteins expressed by cells of the innate immune system, such as dendritic cells, monocytes and epithelial cells, to identify two classes of molecules: pathogen-associated molecular patterns, which are associated with microbial pathogens, damage-associated molecular patterns, which are associated with components of host's cells that are released during cell damage or death. They are called primitive pattern recognition receptors because they evolved before other parts of the immune system before adaptive immunity. PRRs mediate the initiation of antigen-specific adaptive immune response and release of inflammatory cytokines; the microbe-specific molecules that are recognized by a given PRR are called pathogen-associated molecular patterns and include bacterial carbohydrates, nucleic acids, bacterial peptides and lipoteichoic acids, N-formylmethionine and fungal glucans and chitin.
Endogenous stress signals are called damage-associated molecular patterns and include uric acid and extracellular ATP, among many other compounds. There are several subgroups of PRRs, they are classified according to their ligand specificity, localization and/or evolutionary relationships. Based on their localization, PRRs may be divided into cytoplasmic PRRs. Membrane-bound PRRs include Toll like C-type lectin receptors. Cytoplasmic PRRs include RIG-I-like receptors. PRRs were first discovered in plants. Since that time many plant PRRs have been predicted by genomic analysis. Unlike animal PRRs, which associated with intracellular kinases via adaptor proteins, plant PRRs are composed of an extracellular domain, transmembrane domain, juxtamembrane domain and intracellular kinase domain as part of a single protein. Recognition of extracellular or endosomal pathogen-associated molecular patterns is mediated by transmembrane proteins known as toll-like receptors. TLRs share a typical structural motif, the Leucine rich repeats, which give them their specific appearance and are responsible for TLR functionality.
Toll-like receptors were first discovered in Drosophila and trigger the synthesis and secretion of cytokines and activation of other host defense programs that are necessary for both innate or adaptive immune responses. 10 functional members of the TLR family have been described in humans so far. Studies have been conducted on TLR11 as well, it has been shown that it recognizes flagellin and profilin-like proteins in mice. Nonetheless, TLR11 is only a pseudogene in humans without direct function or functional protein expression; each of the TLR has been shown to interact with a specific PAMP. TLRs tend to dimerize, TLR4 forms homodimers, TLR6 can dimerize with either TLR1 or TLR2. Interaction of TLRs with their specific PAMP is mediated through either MyD88- dependent pathway and triggers the signaling through NF-κB and the MAP kinase pathway and therefore the secretion of pro-inflammatory cytokines and co-stimulatory molecules or TRIF - dependent signaling pathway. MyD88 - dependent pathway is induced by various PAMPs stimulating the TLRs on macrophages and dendritic cells.
MyD88 attracts the IRAK4 molecule, IRAK4 recruits IRAK2 to form a signaling complex. The signaling complex reacts with TRAF6 which leads to TAK1 activation and the induction of inflammatory cytokines; the TRIF-dependent pathway is induced by DCs after TLR3 and TLR4 stimulation. Molecules released following TLR activation signal to other cells of the immune system making TLRs key elements of innate immunity and adaptive immunity. Many different cells of the innate immune system express a myriad of CLRs which shape innate immunity by virtue of their pattern recognition ability. Though, most classes of human pathogens are covered by CLRs, CLRs are a major receptor for recognition of fungi: nonetheless, other PAMPs have been identifies in studies as targets of CLRs as well e.g. mannose is the recognition motif for many viruses and mycobacteria. In addition, many of acquired nonself surfaces e.g. carcinoembryonic/oncofetal type neoantigens carrying "internal danger source"/"self turned nonself" type pathogen pattern are identified and destroyed or sequestered by the immune system by virtue of the CLRs.
The name lectin is a bit misleading because the family includes proteins with at least one C-type lectin domain, a specific type of carbohydrate recognition domain. CTLD is a ligand binding motif found in more than 1000 known proteins and the ligands are not sugars. If and when the ligand is sugar they need Ca2+ – hence the name "C-type", but many of them don't have a known sugar ligand thus despite carrying a lectin type fold structure, some of them are technically not "lectin" in function. There are several types of signaling involved in CLRs induced immune response, major connection has been identified between TLR and CLR signaling, therefore we differentiate between TLR-dependent and TLR-independent signaling. DC-SIGN leading to RAF1-MEK-ERK cascade, BDCA2 signaling
Adaptive immune system
The adaptive immune system known as the acquired immune system or, more as the specific immune system, is a subsystem of the overall immune system, composed of specialized, systemic cells and processes that eliminate pathogens or prevent their growth. The acquired immune system is one of the two main immunity strategies found in vertebrates. Acquired immunity creates immunological memory after an initial response to a specific pathogen, leads to an enhanced response to subsequent encounters with that pathogen; this process of acquired immunity is the basis of vaccination. Like the innate system, the acquired system includes both humoral immunity components and cell-mediated immunity components; the term "adaptive" was first used by Robert Good in reference to antibody responses in frogs as a synonym for "acquired immune response" in 1964. Good acknowledged he used the terms as synonyms but explained only that he "preferred" to use the term "adaptive", he might have been thinking of the not implausible theory of antibody formation in which antibodies were plastic and could adapt themselves to the molecular shape of antigens, and/or to the concept of "adaptive enzymes" as described by Monod in bacteria, that is, enzymes whose expression could be induced by their substrates.
The phrase was used exclusively by Good and his students and a few other immunologists working with marginal organisms until the 1990's when it became used in tandem with the term "innate immunity" which became a popular subject after the discovery of the Toll receptor system in Drosophila, a marginal organism for the study of immunology. The term "adaptive" as used in immunology is problematic as acquired immune responses can be both adaptive and maladaptive in the physiological sense. Indeed, both acquired and innate immune responses can be both adaptive and maladaptive in the evolutionary sense. Most textbooks today, following the early use by Janeway, use "adaptive" exclusively and noting in glossaries that the term is synonymous with "acquired"; the classic sense of "acquired immunity" came to mean, since Tonegawas's discovery, "antigen-specific immunity mediated by somatic gene rearrangements that create clone-defining antigen receptors". In the last decade, the term "adaptive" has been applied to another class of immune response not so-far associated with somatic gene rearrangements.
These include expansion of natural killer cells with so-far unexplained specificity for antigens, expansion of NK cells expressing germ-line encoded receptors, activation of other innate immune cells to an activated state that confers a short-term "immune memory". In this sense, "adaptive immunity" more resembles the concept of "activated state" or "heterostasis", thus returning in sense to the physiological sense of "adaptation" to environmental changes. Unlike the innate immune system, the acquired immune system is specific to a particular pathogen. Acquired immunity can provide long-lasting protection. In other cases it does not provide lifetime protection; the acquired system response destroys invading pathogens and any toxic molecules they produce. Sometimes the acquired system is unable to distinguish harmful from harmless foreign molecules. Antigens are any substances; the cells that carry out the acquired immune response are white blood cells known as lymphocytes. Two main broad classes—antibody responses and cell mediated immune response—are carried by two different lymphocytes.
In antibody responses, B cells are activated to secrete antibodies, which are proteins known as immunoglobulins. Antibodies travel through the bloodstream and bind to the foreign antigen causing it to inactivate, which does not allow the antigen to bind to the host. In acquired immunity, pathogen-specific receptors are "acquired" during the lifetime of the organism; the acquired response is called "adaptive" because it prepares the body's immune system for future challenges. The system is adaptable because of somatic hypermutation, VJ recombination; this mechanism allows a small number of genes to generate a vast number of different antigen receptors, which are uniquely expressed on each individual lymphocyte. Since the gene rearrangement leads to an irreversible change in the DNA of each cell, all progeny of that cell inherit genes that encode the same receptor specificity, including the memory B cells and memory T cells that are the keys to long-lived specific immunity. A theoretical framework explaining the workings of the acquired immune system is provided by immune network theory.
This theory, which builds on established concepts of clonal selection, is being applied in the search for an HIV vaccine. Acquired immunity is triggered in vertebrates when a pathogen evades the innate immune system and generates a threshold level of antigen and generates "stranger" or "danger" signals activating dendritic cells; the major functions of the acquired immune system include: Recognition of specific "non-self" antigens in the presence of "self", during the process of antigen presentation. Generation of responses that are tailored to maximally eliminate specific pathoge
International Standard Serial Number
An International Standard Serial Number is an eight-digit serial number used to uniquely identify a serial publication, such as a magazine. The ISSN is helpful in distinguishing between serials with the same title. ISSN are used in ordering, interlibrary loans, other practices in connection with serial literature; the ISSN system was first drafted as an International Organization for Standardization international standard in 1971 and published as ISO 3297 in 1975. ISO subcommittee TC 46/SC 9 is responsible for maintaining the standard; when a serial with the same content is published in more than one media type, a different ISSN is assigned to each media type. For example, many serials are published both in electronic media; the ISSN system refers to these types as electronic ISSN, respectively. Conversely, as defined in ISO 3297:2007, every serial in the ISSN system is assigned a linking ISSN the same as the ISSN assigned to the serial in its first published medium, which links together all ISSNs assigned to the serial in every medium.
The format of the ISSN is an eight digit code, divided by a hyphen into two four-digit numbers. As an integer number, it can be represented by the first seven digits; the last code digit, which may be 0-9 or an X, is a check digit. Formally, the general form of the ISSN code can be expressed as follows: NNNN-NNNC where N is in the set, a digit character, C is in; the ISSN of the journal Hearing Research, for example, is 0378-5955, where the final 5 is the check digit, C=5. To calculate the check digit, the following algorithm may be used: Calculate the sum of the first seven digits of the ISSN multiplied by its position in the number, counting from the right—that is, 8, 7, 6, 5, 4, 3, 2, respectively: 0 ⋅ 8 + 3 ⋅ 7 + 7 ⋅ 6 + 8 ⋅ 5 + 5 ⋅ 4 + 9 ⋅ 3 + 5 ⋅ 2 = 0 + 21 + 42 + 40 + 20 + 27 + 10 = 160 The modulus 11 of this sum is calculated. For calculations, an upper case X in the check digit position indicates a check digit of 10. To confirm the check digit, calculate the sum of all eight digits of the ISSN multiplied by its position in the number, counting from the right.
The modulus 11 of the sum must be 0. There is an online ISSN checker. ISSN codes are assigned by a network of ISSN National Centres located at national libraries and coordinated by the ISSN International Centre based in Paris; the International Centre is an intergovernmental organization created in 1974 through an agreement between UNESCO and the French government. The International Centre maintains a database of all ISSNs assigned worldwide, the ISDS Register otherwise known as the ISSN Register. At the end of 2016, the ISSN Register contained records for 1,943,572 items. ISSN and ISBN codes are similar in concept. An ISBN might be assigned for particular issues of a serial, in addition to the ISSN code for the serial as a whole. An ISSN, unlike the ISBN code, is an anonymous identifier associated with a serial title, containing no information as to the publisher or its location. For this reason a new ISSN is assigned to a serial each time it undergoes a major title change. Since the ISSN applies to an entire serial a new identifier, the Serial Item and Contribution Identifier, was built on top of it to allow references to specific volumes, articles, or other identifiable components.
Separate ISSNs are needed for serials in different media. Thus, the print and electronic media versions of a serial need separate ISSNs. A CD-ROM version and a web version of a serial require different ISSNs since two different media are involved. However, the same ISSN can be used for different file formats of the same online serial; this "media-oriented identification" of serials made sense in the 1970s. In the 1990s and onward, with personal computers, better screens, the Web, it makes sense to consider only content, independent of media; this "content-oriented identification" of serials was a repressed demand during a decade, but no ISSN update or initiative occurred. A natural extension for ISSN, the unique-identification of the articles in the serials, was the main demand application. An alternative serials' contents model arrived with the indecs Content Model and its application, the digital object identifier, as ISSN-independent initiative, consolidated in the 2000s. Only in 2007, ISSN-L was defined in the
B cells known as B lymphocytes, are a type of white blood cell of the lymphocyte subtype. They function in the humoral immunity component of the adaptive immune system by secreting antibodies. Additionally, B cells present secrete cytokines. In mammals, B cells mature in the bone marrow, at the core of most bones. In birds, B cells mature in the bursa of Fabricius, a lymphoid organ.. B cells, unlike the other two classes of lymphocytes, T cells and natural killer cells, express B cell receptors on their cell membrane. BCRs allow the B cell to bind to a specific antigen, against which it will initiate an antibody response. B cells develop from hematopoietic stem cells. HSCs first differentiate into multipotent progenitor cells common lymphoid progenitor cells. From here, their development into B cells occurs in several stages, each marked by various gene expression patterns and immunoglobulin H chain and L chain gene loci arrangements, the latter due to B cells undergoing VJ recombination as they develop.
B cells undergo two types of selection while developing in the bone marrow to ensure proper development. Positive selection occurs through antigen-independent signaling involving both the pre-BCR and the BCR. If these receptors do not bind to their ligand, B cells do not receive the proper signals and cease to develop. Negative selection occurs through the binding of self-antigen with the BCR; this negative selection process leads to a state of central tolerance, in which the mature B cells don't bind with self antigens present in the bone marrow. To complete development, immature B cells migrate from the bone marrow into the spleen as transitional B cells, passing through two transitional stages: T1 and T2. Throughout their migration to the spleen and after spleen entry, they are considered T1 B cells. Within the spleen, T1 B cells transition to T2 B cells. T2 B cells differentiate into either follicular B cells or marginal zone B cells depending on signals received through the BCR and other receptors.
Once differentiated, they are now considered naive B cells. B cell activation occurs in the secondary lymphoid organs, such as the lymph nodes. After B cells mature in the bone marrow, they migrate through the blood to SLOs, which receive a constant supply of antigen through circulating lymph. At the SLO, B cell activation begins when the B cell binds to an antigen via its BCR. Although the events taking place after activation have yet to be determined, it is believed that B cells are activated in accordance with the kinetic segregation model determined in T lymphocytes; this model denotes that before antigen stimulation, receptors diffuse through the membrane coming into contact with Lck and CD45 in equal frequency, rendering a net equilibrium of phosphorylation and non-phosphorylation. It is only when the cell comes in contact with an antigen presenting cell that the larger CD45 is displaced due to the close distance between the two membranes; this allows for net phosphorylation of the BCR and the initiation of the signal transduction pathway.
Of the three B cell subsets, FO B cells preferentially undergo T cell-dependent activation while MZ B cells and B1 B cells preferentially undergo T cell-independent activation. B cell activation is enhanced through the activity of CD21, a surface receptor in complex with surface proteins CD19 and CD81; when a BCR binds an antigen tagged with a fragment of the C3 complement protein, CD21 binds the C3 fragment, co-ligates with the bound BCR, signals are transduced through CD19 and CD81 to lower the activation threshold of the cell. It has been shown that CD20 is directly required for BCR signalling in B cells, therapeutically used anti-CD20 antibodies such rituximab eliminate the B cells that have a high potential for activation of the BCR signalling pathway, it has been described that BCR signalling and B cell activation is inhibited by p53 stabilization during DNA damage response. Antigens that activate B cells with the help of T-cell are known as T cell-dependent antigens and include foreign proteins.
They are named as such because they are unable to induce a humoral response in organisms that lack T cells. B cell response to these antigens takes multiple days, though antibodies generated have a higher affinity and are more functionally versatile than those generated from T cell-independent activation. Once a BCR binds a TD antigen, the antigen is taken up into the B cell through receptor-mediated endocytosis and presented to T cells as peptide pieces in complex with MHC-II molecules on the cell membrane. T helper cells follicular T helper cells, that were activated with the same antigen recognize and bind these MHC-II-peptide complexes through their T cell receptor. Following TCR-MHC-II-peptide binding, T cells express the surface protein CD40L as well as cytokines such as IL-4 and IL-21. CD40L serves as a necessary co-stimulatory factor for B cell activation by binding the B cell surface receptor CD40, which promotes B cell proliferation, immunoglobulin class switching, somatic hypermutation as well as sustains T cell growth and differentiation.
T cell-derived cytokines bound