Open AccessMarginal zone B cells are naturally reactive to collagen type II and are involved in the initiation of the immune response in collagen-induced arthritis
Author(s) -
Cecilia Carnrot,
Kajsa E. Prokopec,
Kristina Råsbo,
Mikael C. I. Karlsson,
Sandra Kleinau
Publication year - 2011
Publication title -
cellular and molecular immunology/cellular and molecular immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.5
H-Index - 81
eISSN - 2042-0226
pISSN - 1672-7681
DOI - 10.1038/cmi.2011.2
Subject(s) - marginal zone , spleen , immunology , b cell , immunization , immune system , arthritis , biology , b 1 cell , antigen , antibody , t cell , microbiology and biotechnology , antigen presenting cell
Antibodies against type II collagen (CII) are essential for development of collagen-induced arthritis (CIA), but how and where the B-cell response to CII is initiated is not fully known. We show here that naive DBA/1 mice display naturally reactive IgM and IgG anti-CII producing B cells prior to immunization. The CII-reactive B cells were observed in the spleen and recognized as marginal zone (MZ) B cells. After CII immunization, CII-specific B cells expanded rapidly in the spleen, in contrast to the lymph nodes, with the initial response derived from MZ B cells and later by follicular (FO) B cells. This was evident despite that the MZ B cells were subject to stringent tolerance mechanisms by having a greater Fc gamma receptor IIb expression than the FO B cells. Further, the MZ B cells migrated to the FO areas upon immunization, possibly providing antigen and activating FO T cells and subsequently FO B cells. Thus, around CIA onset increased numbers of IgG anti-CII producing FO B cells was seen in the spleen, which was dominated by IgG2a- and IgG2b-positive cells. These data demonstrate that CII-reactive MZ B cells are present before and expand after CII immunization, suggesting an initiating role of MZ B cells in the development of CIA.