FCRL3 promotes TLR9-induced B-cell activation and suppresses plasma cell differentiation

Fu Jun Li, Daniel M. Schreeder, Ran Li, Jiongru Wu, Randall S. Davis

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

Fc receptor-like (FCRL) molecules are preferentially expressed by B lymphocytes and possess tyrosine-based immunoregulatory function. Although they generally inhibit B-cell receptor signaling, their influence on other activation pathways remains largely unexplored. In humans, FCRL3 encodes a type I transmembrane protein harboring both cytoplasmic ITAM and ITIM elements that can repress B-cell receptor activation. Despite this inhibitory property, mounting associations for FCRL3 with autoimmune and lympho-proliferative disorders imply a role for it in promoting B-cell pathogenesis. Here, we explore the influence of FCRL3 on B-cell responses to innate TLR9 stimulation. A detailed survey of blood B-cell populations found that FCRL3 expression increased as a function of differentiation and was higher among memory subsets with innate-like features. FCRL3 ligation augmented CpG oligodeoxynucleotide TLR9-mediated B-cell proliferation, activation, and survival, but surprisingly, abrogated plasma cell differentiation and antibody production. Although FCRL3 amplified the NF-κB and mitogen-activated protein kinase signaling cascades, it halted CpG triggered BLIMP1 induction in an ERK-dependent fashion. These findings indicate that FCRL3 differentially modulates innate signaling in B cells and provide new insight into the potential of this disease-associated receptor to counter-regulate adaptive and innate immunity.

Original languageEnglish (US)
Pages (from-to)2980-2992
Number of pages13
JournalEuropean Journal of Immunology
Volume43
Issue number11
DOIs
StatePublished - Nov 2013

Keywords

  • B cells
  • Fc receptor-like
  • Plasma cell differentiation
  • TLR

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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