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 naı¨ve 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 wer... More
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 naı¨ve 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 Fcγ 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.
