TY - JOUR
T1 - Deregulation of peripheral B-cell development in enhanced severity of collagen-induced arthritis in FcγRIIB-deficient mice
AU - Nakamura, Akira
AU - Nukiwa, Toshihiro
AU - Takai, Toshiyuki
N1 - Funding Information:
We thank M. Ono and S. Mori for helpful discussion, and A. Sugahara, T. Yuasa, and K. Yajima for technical support. This work was supported by the CREST Program of Japan Science and Technology Corporation (JST) and the Grant-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology of Japan (to T.T).
PY - 2003/5
Y1 - 2003/5
N2 - Accumulating evidence indicates that the type IIB Fc receptor for IgG (FcγRIIB) 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 FcγRIIB-deficient mice. To clarify the role of FcγRIIB in the emergence of autoreactive B cells, we analyzed B-cell compartments in the autoimmune arthritis-susceptible DBA/1 mice devoid of FcγRIIB (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-1α 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 FcγRIIB-dependent triple regulation in the peripheral T2 B cells, in the antibody production, and in the effector cell responses is crucial for suppressing CIA.
AB - Accumulating evidence indicates that the type IIB Fc receptor for IgG (FcγRIIB) 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 FcγRIIB-deficient mice. To clarify the role of FcγRIIB in the emergence of autoreactive B cells, we analyzed B-cell compartments in the autoimmune arthritis-susceptible DBA/1 mice devoid of FcγRIIB (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-1α 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 FcγRIIB-dependent triple regulation in the peripheral T2 B cells, in the antibody production, and in the effector cell responses is crucial for suppressing CIA.
KW - Autoantibody
KW - B lymphocytes
KW - Cellular differentiation
KW - Collagen-induced arthritis
KW - Fc receptor
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U2 - 10.1016/S0896-8411(03)00034-9
DO - 10.1016/S0896-8411(03)00034-9
M3 - Article
C2 - 12753808
AN - SCOPUS:0037725010
VL - 20
SP - 227
EP - 236
JO - Journal of Autoimmunity
JF - Journal of Autoimmunity
SN - 0896-8411
IS - 3
ER -