Journal
JOURNAL OF EXPERIMENTAL MEDICINE
Volume 207, Issue 12, Pages 2767-2778Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20100171
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- Max-Planck-Institute for Infection Biology in Berlin
- Deutsche Forschungsgemeinschaft [EH221-4, WA2590-2]
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Abnormalities in expression levels of the IgG inhibitory Fc gamma receptor IIB (Fc gamma 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 gamma RIIB-deficient mice. We found that loss of Fc gamma 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 gamma 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 gamma RIIB-independent checkpoint for autoreactivity between the GC and the plasma cell compartment.
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