Deregulation of peripheral B-cell development in enhanced severity of collagen-induced arthritis in FcgammaRIIB-deficient mice.
Accumulating evidence indicates that the type IIB Fc receptor for IgG (FcgammaRIIB) plays a pivotal role in maintaining peripheral tolerance by suppressing excessive humoral and cellular immune responses. However, little is known about the mechanism by which the autoreactive B cells develop in the periphery in FcgammaRIIB-deficient mice. To clarify the role of FcgammaRIIB in the emergence of autoreactive B cells, we analyzed B-cell compartments in the autoimmune arthritis-susceptible DBA/1 mice devoid of FcgammaRIIB (DBA.IIB-/-) during the induction of collagen-induced arthritis (CIA). We found that DBA.IIB-/- showed an increase in the number of peripheral immature type 2 transitional (T2) B cells after immunization with type II collagen (C-II), followed by the enhanced severity of CIA with higher autoantibody titers to mouse C-II than those of wild-type DBA/1. In addition, elevated secretion of IL-1alpha by peritoneal macrophages from DBA.IIB-/- on stimulation with IgG immune complexes in vitro suggested the augmented effector cell responses in the CIA course of DBA.IIB-/-. These findings suggest that the FcgammaRIIB-dependent triple regulation in the peripheral T2 B cells, in the antibody production, and in the effector cell responses is crucial for suppressing CIA.
Nakamura
Akira
A
Department of Experimental Immunology, Institute of Development, Aging and Cancer, Tohoku University, Seiryo-machi 4-1, Sendai 980-8575, Japan.
Nukiwa
Toshihiro
T
Takai
Toshiyuki
T
D000818:Animals; D015703:Antigens, CD / Q000235:genetics; D017209:Apoptosis; D001169:Arthritis, Experimental / Q000276:immunology* / Q000473:pathology*; D001323:Autoantibodies / Q000096:biosynthesis; D015551:Autoimmunity; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000473:pathology*; D002454:Cell Differentiation; D024043:Collagen Type II / Q000276:immunology; D018858:Germinal Center / Q000276:immunology / Q000473:pathology; D007111:Immunity, Cellular; D007375:Interleukin-1 / Q000096:biosynthesis; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D017452:Receptors, IgG / Q000172:deficiency* / Q000235:genetics; D017634:Self Tolerance
D015703:Antigens, CD; D001323:Autoantibodies; D024043:Collagen Type II; C080571:Fc gamma receptor IIB; D007375:Interleukin-1; D017452:Receptors, IgG