Development of self-reactive germinal center B cells and plasma cells in autoimmune Fc gammaRIIB-deficient mice.

ABSTRACT: Abnormalities in expression levels of the IgG inhibitory Fc gamma receptor IIB (Fc?RIIB) are associated with the development of immunoglobulin (Ig) G serum autoantibodies and systemic autoimmunity in mice and humans. We used Ig gene cloning from single isolated B cells to examine the checkpoints that regulate development of autoreactive germinal center (GC) B cells and plasma cells in Fc?RIIB-deficient mice. We found that loss of Fc?RIIB was associated with an increase in poly- and autoreactive IgG(+) GC B cells, including hallmark anti-nuclear antibody-expressing cells that possess characteristic Ig gene features and cells producing kidney-reactive autoantibodies. In the absence of Fc?RIIB, autoreactive B cells actively participated in GC reactions and somatic mutations contributed to the generation of highly autoreactive IgG antibodies. In contrast, the frequency of autoreactive IgG(+) B cells was much lower in spleen and bone marrow plasma cells, suggesting the existence of an Fc?RIIB-independent checkpoint for autoreactivity between the GC and the plasma cell compartment.

SUBMITTER: Tiller T 

PROVIDER: S-EPMC2989760 | biostudies-literature | 2010 Nov

REPOSITORIES: biostudies-literature