title: Quorum sensing contributes to activated IgM-secreting B cell homeostasis.
abstract: Maintenance of plasma IgM levels is critical for immune system function and homeostasis in humans and mice. However, the mechanisms that control homeostasis of the activated IgM-secreting B cells are unknown. After adoptive transfer into immune-deficient hosts, B lymphocytes expand poorly, but fully reconstitute the pool of natural IgM-secreting cells and circulating IgM levels. By using sequential cell transfers and B cell populations from several mutant mice, we were able to identify novel mechanisms regulating the size of the IgM-secreting B cell pool. Contrary to previous mechanisms described regulating homeostasis, which involve competition for the same niche by cells having overlapping survival requirements, homeostasis of the innate IgM-secreting B cell pool is also achieved when B cell populations are able to monitor the number of activated B cells by detecting their secreted products. Notably, B cell populations are able to assess the density of activated B cells by sensing their secreted IgG. This process involves the FcγRIIB, a low-affinity IgG receptor that is expressed on B cells and acts as a negative regulator of B cell activation, and its intracellular effector the inositol phosphatase SHIP. As a result of the engagement of this inhibitory pathway, the number of activated IgM-secreting B cells is kept under control. We hypothesize that malfunction of this quorum-sensing mechanism may lead to uncontrolled B cell activation and autoimmunity.
authors.affiliation: Unité de Biologie des Populations Lymphocytaires, Départment d'Immunologie, Institut Pasteur, Paris 75015, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Montaudouin
authors.forename: Marie
authors.initials: M
authors.lastname: Anson
authors.forename: Yi
authors.initials: Y
authors.lastname: Hao
authors.forename: Susanne V
authors.initials: SV
authors.lastname: Duncker
authors.forename: Tahia
authors.initials: T
authors.lastname: Fernandez
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Gaudin
authors.forename: Michael
authors.initials: M
authors.lastname: Ehrenstein
authors.forename: William G
authors.initials: WG
authors.lastname: Kerr
authors.forename: Jean-Hervé
authors.initials: JH
authors.lastname: Colle
authors.forename: Pierre
authors.initials: P
authors.lastname: Bruhns
authors.forename: Marc
authors.initials: M
authors.lastname: Daëron
authors.forename: António A
authors.initials: AA
authors.lastname: Freitas
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism* / Q000637:transplantation; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D006706:Homeostasis / Q000235:genetics / Q000276:immunology*; D007074:Immunoglobulin G / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053038:Quorum Sensing / Q000235:genetics / Q000276:immunology*
chemical_list: D007074:Immunoglobulin G; D007075:Immunoglobulin M