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10.1038/cmi.2015.37

http://scihub22266oqcxt.onion/10.1038/cmi.2015.37
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C4496548!4496548!25958842
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suck abstract from ncbi


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pmid25958842      Cell+Mol+Immunol 2015 ; 12 (4): 493-504
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  • Function and regulation of self-reactive marginal zone B cells in autoimmune arthritis #MMPMID25958842
  • Palm AKE; Friedrich HC; Mezger A; Salomonsson M; Myers LK; Kleinau S
  • Cell Mol Immunol 2015[Jul]; 12 (4): 493-504 PMID25958842show ga
  • Polyreactive innate-type B cells account for many B cells expressing self-reactivity in the periphery. Improper regulation of these B cells may be an important factor that underlies autoimmune disease. Here we have explored the influence of self-reactive innate B cells in the development of collagen-induced arthritis (CIA), a mouse model of rheumatoid arthritis. We show that splenic marginal zone (MZ), but not B-1 B cells exhibit spontaneous IgM reactivity to autologous collagen II in naïve mice. Upon immunization with heterologous collagen II in complete Freund's adjuvant the collagen-reactive MZ B cells expanded rapidly, while the B-1 B cells showed a modest anti-collagen response. The MZ B cells were easily activated by toll-like receptor (TLR) 4 and 9-ligands in vitro, inducing proliferation and cytokine secretion, implying that dual engagement of the B-cell receptor and TLRs may promote the immune response to self-antigen. Furthermore, collagen-primed MZ B cells showed significant antigen-presenting capacity as reflected by cognate T-cell proliferation in vitro and induction of IgG anti-collagen antibodies in vivo. MZ B cells that were deficient in complement receptors 1 and 2 demonstrated increased proliferation and cytokine production, while Fc? receptor IIb deficiency of the cells lead to increased cytokine production and antigen presentation. In conclusion, our data highlight self-reactive MZ B cells as initiators of the autoimmune response in CIA, where complement and Fc receptors are relevant in controlling the self-reactivity in the cells.
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