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BAFF receptor and TACI in B‐1b cell maintenance and antibacterial responses
Author(s) -
Dickinson Gregory S.,
Akkoyunlu Mustafa,
Bram Richard J.,
Alugupalli Kishore R.
Publication year - 2015
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/nyas.12772
Subject(s) - b cell activating factor , b cell , cd19 , breakpoint cluster region , b cell receptor , microbiology and biotechnology , immunology , bruton's tyrosine kinase , signal transduction , biology , toll like receptor , receptor , immune system , innate immune system , antibody , genetics , tyrosine kinase
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.