Regulatory B cells

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Regulatory B cells (Bregs) represent a small population of B cells which participates in immunomodulations and in suppression of immune responses. These cells regulate the immune system by different mechanisms, the main mechanism is a production of anti-inflammatory cytokine interleukin 10 (IL-10). The regulatory effects of Bregs were described in various models of inflammation, autoimmune diseases, transplantation reactions and in anti-tumor immunity.


In the 1970s it was noticed that Bregs could suppress immune reaction independently of antibody production;[1] in 1996 Janeway´s group observed an immunomodulation of experimental autoimmune encephalomyelitis (EAE) by B cells.[2] Similar results were shown in a model of chronic colitis one year later.[3] Then a role of Bregs was found in many mouse models of autoimmune diseases as rheumatoid arthritis[4] or systemic lupus erythematosus (SLE).[5]

Development and Breg populations[edit]

Bregs can develop from different subsets of B cells. Whether Breg cells uniquely derive from a specific progenitor or originate within conventional B cell subsets is still an open question.[6] Bregs shared many markers with various B cells subsets due to their origin. Mouse Bregs were mainly CD5 and CD1d positive in model of EAE or after exposition of Leishmania major.[7][8] By contrast mouse Bregs in model of collagen-induced arthritis (CIA) were mainly CD21 and CD23 positive.[9] Breg were found in human, too. Markers of peripheral blood Bregs were molecules CD24 and CD38.[10] However, peripheral blood Bregs were mostly CD24 and CD27 positive after cultivation with anti-CD40 antibody and CpG bacterial DNA,[11] they were also positive for CD25, CD71 and PD-L1 after stimulation by CpG bacterial DNA and through TLR9.[12]

Mechanisms of Breg action[edit]

There are several mechanisms of Breg action. Nevertheless, the most examined mechanism is production of IL-10. IL-10 has strong anti-inflammatory effects.[13][14] and it inhibits or suppresses inflammatory reactions mediated by T cells, especially Th1 type immune reactions. This was shown for example in model EAE,[15] CIA[16] or contact hypersensitivity.[17] Likewise, regulatory B cell subsets have also been demonstrated to inhibit Th1 responses through IL-10 production during chronic infectious diseases such as visceral leishmaniasis.[18] Next suppressive Breg mechanism is production of transforming growth factor (TGF-β), another anti-inflammatory cytokine.[13] Role of Bregs producing TGF-β was found in mouse of models of SLE [5] and diabetes.[19] Another mechanism of Breg acting involves surface molecules, for example FasL[20] or PD-L1,[18][21] which cause death of target cells.


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  2. ^ Wolf, SD; Dittel, BN; Hardardottir, F; Janeway CA, Jr (Dec 1, 1996). "Experimental autoimmune encephalomyelitis induction in genetically B cell-deficient mice". The Journal of Experimental Medicine. 184 (6): 2271–8. doi:10.1084/jem.184.6.2271. PMC 2196394Freely accessible. PMID 8976182. 
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