title: Marginal zone B cells are naturally reactive to collagen type II and are involved in the initiation of the immune response in collagen-induced arthritis.
abstract: 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.
authors.affiliation: Department of Cell and Molecular Biology, Uppsala University, Uppsala, Sweden.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Carnrot
authors.forename: Kajsa E
authors.initials: KE
authors.lastname: Prokopec
authors.forename: Kristina
authors.initials: K
authors.lastname: Råsbo
authors.forename: Mikael Ci
authors.initials: MC
authors.lastname: Karlsson
authors.forename: Sandra
authors.initials: S
authors.lastname: Kleinau
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D024043:Collagen Type II / Q000276:immunology*; D005260:Female; D007108:Immune Tolerance / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D007075:Immunoglobulin M / Q000097:blood / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D016688:Mice, Inbred NOD; D013154:Spleen / Q000276:immunology
chemical_list: D024043:Collagen Type II; D007074:Immunoglobulin G; D007075:Immunoglobulin M