Deregulation of peripheral B-cell development in enhanced severity of collagen-induced arthritis in FcγRIIB-deficient mice

Akira Nakamura, Toshihiro Nukiwa, Toshiyuki Takai

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)227-236
Number of pages10
JournalJournal of Autoimmunity
Volume20
Issue number3
DOIs
Publication statusPublished - 2003 May

Keywords

  • Autoantibody
  • B lymphocytes
  • Cellular differentiation
  • Collagen-induced arthritis
  • Fc receptor

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint

Dive into the research topics of 'Deregulation of peripheral B-cell development in enhanced severity of collagen-induced arthritis in FcγRIIB-deficient mice'. Together they form a unique fingerprint.

Cite this