title: BAFF receptor and TACI in B-1b cell maintenance and antibacterial responses.
abstract: Although evidence of the protective immunity conferred by B-1b cells (CD19(+) B220(+) IgM(hi) Mac1(+) CD5(-)) has been established, the mechanisms governing the maintenance and activation of B-1b cells following pathogen encounter remain unclear. B cell-activating factor (BAFF) and a proliferation-inducing ligand (APRIL) mediate their function in mature B cells through the BAFF receptor (BAFFR) and transmembrane activator and CAML interactor (TACI). BAFFR-deficient mice have lower numbers of B-1b cells, and this reduction is directly proportional to BAFFR levels. The generation of B-1b cells is also dependent on the strength of B cell receptor (BCR) signaling. Mice with impaired BCR signaling, such as X-linked immunodeficient (xid) mice, have B-1b cell deficiency, indicating that both BCR- and BAFFR-mediated signaling are critical for B-1b cell homeostasis. Borrelia hermsii induces expansion and persistence of B-1b cells in xid mice, and these B-1b cells provide a heightened protective response. Toll-like receptor (TLR)-mediated stimulation of xid B cells results in a significant increase in TACI expression and restoration of TACI-mediated functions. The activation of TLR signaling by B. hermsii and BCR/TLR costimulation-mediated upregulation of BAFFR and TACI on B-1b cells suggests that B-1b cell maintenance and function following bacterial exposure may depend on BAFFR- and TACI-mediated signaling. In fact, the loss of both BAFFR and TACI results in a greater impairment in anti-B. hermsii responses compared to deficiency of BAFFR or TACI alone.
authors.affiliation: Department of Microbiology and Immunology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania.
authors.forename: Gregory S
authors.initials: GS
authors.lastname: Dickinson
authors.affiliation: Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Mustafa
authors.initials: M
authors.lastname: Akkoyunlu
authors.affiliation: Department of Pediatrics and Adolescent Medicine, College of Medicine, Mayo Clinic, Rochester, Minnesota.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Bram
authors.affiliation: Department of Microbiology and Immunology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania.
authors.forename: Kishore R
authors.initials: KR
authors.lastname: Alugupalli
mesh_terms: D000818:Animals; D053264:B-Cell Activating Factor / Q000378:metabolism; D053265:B-Cell Activation Factor Receptor / Q000378:metabolism*; D016175:B-Lymphocyte Subsets / Q000378:metabolism* / Q000382:microbiology*; D006801:Humans; D056724:Immunity, Humoral / Q000502:physiology; D053303:Transmembrane Activator and CAML Interactor Protein / Q000378:metabolism*
chemical_list: D053264:B-Cell Activating Factor; D053265:B-Cell Activation Factor Receptor; C435926:TNFRSF13C protein, human; C505719:TNFSF13B protein, human; D053303:Transmembrane Activator and CAML Interactor Protein
keywords: B-1b cells; BAFF receptor; Borrelia hermsii; TACI; Toll-like receptor; X-linked immunodeficiency; polysaccharide vaccines