Browsing by Author "Rawlings, David J."

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    FcγRIIb and BAFF Differentially Regulate Peritoneal B1 Cell Survival
    (2012) Amezcua Vesely, Maria C.; Schwartz, Marc; Bermejo, Daniela A.; Montes, Carolina L.; Cautivo, Kelly M.; Kalergis, Alexis M.; Rawlings, David J.; Acosta-Rodriguez, Eva V.; Gruppi, Adriana
    B1 cells produce most natural Abs in unimmunized mice and play a key role in the response to thymus-independent Ags and microbial infection. Enlargement of B1 cell number in mice is often associated with autoimmunity. However, the factors that control peripheral B1 cell survival remain poorly characterized. Mice lacking the inhibitory receptor Fe gamma RIIb exhibit a massive expansion in peritoneal B1 cells, implicating this receptor in B1 cell homeostasis. In this study, we show that peritoneal B1 cells express the highest levels of Fc gamma RIIb among B cell subsets and are highly susceptible to Fe gamma RIIb-mediated apoptosis. B1 cells upregulate Fc gamma RIIb in response to innate signals, including CpG, and the B cell homeostatic cytokine BAFF efficiently protects activated B1 cells from Fc gamma IIb-mediated apoptosis via receptor downregulation. BAFF-transgenic mice manifest an expansion of peritoneal B1 cells that express lower levels of Fc gamma RIIb and exhibit reduced susceptibility to apoptosis. Whereas both peritoneal B1 cells from wild-type and BAFF-transgenic mice immunized with CpG exhibit an increase in Fc gamma RIIb levels, this change is blunted in BAFF-transgenic animals. Our combined results demonstrate that Fc gamma RIIb controls peritoneal B1 cell survival and this program can be modulated. by the BAFF signaling axis. The Journal of Immunology, 2012, 188: 4792-4800.