BAFF receptor and TACI in B-1b cell maintenance and antibacterial responses

Gregory S. Dickinson, Mustafa Akkoyunlu, Richard J. Bram, Kishore R. Alugupalli

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

Although evidence of the protective immunity conferred by B-1b cells (CD19+B220+IgMhiMac1+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.

Original languageEnglish (US)
Pages (from-to)57-67
Number of pages11
JournalAnnals of the New York Academy of Sciences
Volume1362
Issue number1
DOIs
StatePublished - Dec 1 2015

Keywords

  • B-1b cells
  • BAFF receptor
  • Borrelia hermsii
  • Polysaccharide vaccines
  • TACI
  • Toll-like receptor
  • X-linked immunodeficiency

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science

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