title: FcγRIIb and BAFF differentially regulate peritoneal B1 cell survival.
abstract: 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 FcγRIIb 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 FcγRIIb among B cell subsets and are highly susceptible to FcγRIIb-mediated apoptosis. B1 cells upregulate FcγRIIb in response to innate signals, including CpG, and the B cell homeostatic cytokine BAFF efficiently protects activated B1 cells from FcγRIIb-mediated apoptosis via receptor downregulation. BAFF-transgenic mice manifest an expansion of peritoneal B1 cells that express lower levels of FcγRIIb 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 FcγRIIb levels, this change is blunted in BAFF-transgenic animals. Our combined results demonstrate that FcγRIIb controls peritoneal B1 cell survival and this program can be modulated by the BAFF signaling axis.
authors.affiliation: Centro de Investigaciones en Bioquímica Clínica e Inmunología, Consejo Nacional de Investigaciones Científicas y Técnicas, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba CP 5000, Argentina.
authors.forename: María C
authors.initials: MC
authors.lastname: Amezcua Vesely
authors.forename: Marc
authors.initials: M
authors.lastname: Schwartz
authors.forename: Daniela A
authors.initials: DA
authors.lastname: Bermejo
authors.forename: Carolina L
authors.initials: CL
authors.lastname: Montes
authors.forename: Kelly M
authors.initials: KM
authors.lastname: Cautivo
authors.forename: Alexis M
authors.initials: AM
authors.lastname: Kalergis
authors.forename: David J
authors.initials: DJ
authors.lastname: Rawlings
authors.forename: Eva V
authors.initials: EV
authors.lastname: Acosta-Rodríguez
authors.forename: Adriana
authors.initials: A
authors.lastname: Gruppi
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D053264:B-Cell Activating Factor / Q000096:biosynthesis / Q000172:deficiency / Q000502:physiology*; D016175:B-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D002470:Cell Survival / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D020022:Genetic Predisposition to Disease / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D016513:Mice, SCID; D008822:Mice, Transgenic; D010529:Peritoneal Cavity / Q000166:cytology; D017452:Receptors, IgG / Q000096:biosynthesis / Q000172:deficiency / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology
chemical_list: D053264:B-Cell Activating Factor; C080571:Fc gamma receptor IIB; D017452:Receptors, IgG; C505720:Tnfsf13b protein, mouse