Function and regulation of self-reactive marginal zone B cells in autoimmune arthritis
2015 (English)In: Cellular & Molecular Immunology, ISSN 1672-7681, E-ISSN 2042-0226, Vol. 12, no 4, 493-504 p.Article in journal (Refereed) Published
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 naive mice. Upon immunization with heterologous collagen II in complete Freund's adjuvant the collagen-reactiveMZ 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 gamma 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.
Place, publisher, year, edition, pages
2015. Vol. 12, no 4, 493-504 p.
arthritis, complement receptors, Fc receptors, marginal zone B cells, mice
IdentifiersURN: urn:nbn:se:uu:diva-264328DOI: 10.1038/cmi.2015.37ISI: 000360939000012PubMedID: 25958842OAI: oai:DiVA.org:uu-264328DiVA: diva2:861055
FunderSwedish Research CouncilSwedish Rheumatism Association