title: BLyS receptor signatures resolve homeostatically independent compartments among naïve and antigen-experienced B cells.
abstract: The BLyS family of receptors includes two cytokines, BLyS and APRIL; and three receptors, BR3, BCMA and TACI. Together, these regulate the size and composition of peripheral B cell pools. The multiplicity of ligand-receptor sets, in conjunction with differential receptor expression, alternative binding partners and disparate downstream signaling characteristics, affords the potential to establish independently regulated homeostatic niches among primary and antigen-experienced B cell subsets. Thus, BLyS signaling via BR3 is the dominant homeostatic regulator of primary B cell pools, whereas APRIL interactions with BCMA likely govern memory B cell populations. Short-lived antibody forming cell populations and their proliferating progenitors express a TACI-predominant signature. Further, within each niche, relative fitness to compete for available cytokine is determined by exogenous inputs via adaptive and innate receptor systems, affording intramural hierarchies that determine clonotype composition.
authors.affiliation: Department of Pathology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6082, USA.
authors.forename: Laura S
authors.initials: LS
authors.lastname: Treml
authors.forename: Jenni E
authors.initials: JE
authors.lastname: Crowley
authors.forename: Michael P
authors.initials: MP
authors.lastname: Cancro
mesh_terms: D000818:Animals; D000917:Antibody Formation / Q000276:immunology*; D000941:Antigens / Q000276:immunology; D053264:B-Cell Activating Factor / Q000276:immunology*; D053265:B-Cell Activation Factor Receptor / Q000276:immunology*; D053301:B-Cell Maturation Antigen / Q000276:immunology; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D002455:Cell Division; D002470:Cell Survival; D016207:Cytokines / Q000502:physiology; D006706:Homeostasis; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology*; D051379:Mice; D053303:Transmembrane Activator and CAML Interactor Protein / Q000276:immunology; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13 / Q000276:immunology*
chemical_list: D000941:Antigens; D053264:B-Cell Activating Factor; D053265:B-Cell Activation Factor Receptor; D053301:B-Cell Maturation Antigen; D016207:Cytokines; C108467:TNFRSF13B protein, human; C435926:TNFRSF13C protein, human; C086966:TNFRSF17 protein, human; C114631:TNFSF13 protein, human; C505719:TNFSF13B protein, human; C486361:Tnfrsf13b protein, mouse; C486662:Tnfrsf13c protein, mouse; C490176:Tnfrsf17 protein, mouse; C491959:Tnfsf13 protein, mouse; C505720:Tnfsf13b protein, mouse; D053303:Transmembrane Activator and CAML Interactor Protein; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13