title: B-lymphocyte tolerance and effector function in immunity and autoimmunity.
abstract: B-lymphocytes are integral to host defense against microbial pathogens and are associated with many autoimmune diseases. The B-cell receptor implements B-cell self-tolerance based on the antigen specificity, and B-cell-activating factor receptor (BAFF-R) imposes homeostatic control. While shaping the repertoire, the immune tolerance process also culls mature B cells into distinct populations. The activation response of B cells is tailored to the type of pathogen attack and is facilitated by T-cell help via CD40/CD40L interaction and/or innate cell help via toll-like receptors in conjunction with BAFF receptors and ligands. Activated effector B cells not only produce antibodies, but also produce a variety of cytokines to enhance and suppress the immune response. Not surprisingly, B cells play multiple roles in both humoral and cellular immune responses during infection and autoimmune pathogenesis. Here, we discuss how gene expression and signaling networks regulate peripheral B-cell tolerance, B-cell effector functions and emerging therapies targeting B-cell signaling in autoimmune diseases.
authors.affiliation: Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, FL, 33136, USA, wnkhan@med.miami.edu.
authors.forename: Wasif N
authors.initials: WN
authors.lastname: Khan
authors.forename: Jacqueline A
authors.initials: JA
authors.lastname: Wright
authors.forename: Eden
authors.initials: E
authors.lastname: Kleiman
authors.forename: Justin C
authors.initials: JC
authors.lastname: Boucher
authors.forename: Iris
authors.initials: I
authors.lastname: Castro
authors.forename: Emily S
authors.initials: ES
authors.lastname: Clark
mesh_terms: D000077329:Agammaglobulinaemia Tyrosine Kinase; D000818:Animals; D017209:Apoptosis / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology / Q000378:metabolism; D015551:Autoimmunity; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D007108:Immune Tolerance; D007109:Immunity; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D011947:Receptors, Antigen, B-Cell; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase