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Eur J Immunol. 2013 Nov;43(11):2980-92. doi: 10.1002/eji.201243068. Epub 2013 Aug 12.

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

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  • 1Division of Hematology/Oncology, University of Alabama at Birmingham, Birmingham, AL, USA; Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.

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.

© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

KEYWORDS:

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

PMID:
23857366
[PubMed - indexed for MEDLINE]
PMCID:
PMC3838486
Free PMC Article
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