FcγRIIB Regulation of BCR/TLR-Dependent Autoreactive B Cell Responses

Ana M Avalos; Melissa B Uccellini; Petar Lenert; Gregory A Viglianti; Ann Marshak-Rothstein

doi:10.1002/eji.200940184

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FcγRIIB Regulation of BCR/TLR-Dependent Autoreactive B Cell Responses

Journal article

Open access

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FcγRIIB Regulation of BCR/TLR-Dependent Autoreactive B Cell Responses

Ana M Avalos, Melissa B Uccellini, Petar Lenert, Gregory A Viglianti and Ann Marshak-Rothstein

European journal of immunology, Vol.40(10), pp.2692-2698

10/2010

DOI: 10.1002/eji.200940184

PMCID: PMC3060940

PMID: 20809520

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Abstract

Crosslinking of FcγRIIB and the BCR by immune complexes (ICs) can downregulate antigen-specific B cell responses. Accordingly, FcγRIIB deficiencies have been associated with B cell hyperactivity in patients with SLE and mouse models of lupus. However, we have previously shown that murine IgG2a-autoreactive AM14 B cells respond robustly to chromatin- associated ICs through a mechanism dependent on both the BCR and endosomal TLR9, despite FcγRIIB coexpression. To further evaluate the potential contribution of FcγRIIB to the regulation of autoreactive B cells, we have now compared the IC-triggered responses of FcγRIIB-deficient and FcγRIIB-sufficient AM14 B cells. We find that FcγRIIB-deficient cells respond significantly better than FcγRIIB-sufficient cells when stimulated with DNA ICs that incorporate low affinity TLR9 ligand (CG-poor dsDNA fragments). AM14 B cells also respond to RNA-associated ICs through BCR/TLR7 coengagement, but such BCR/TLR7 dependent responses are normally highly dependent on IFNα costimulation. However, we now show that AM14 FcγRIIB -/- B cells are very effectively activated by RNA ICs without supplemental IFNα priming. These results demonstrate that FcγRIIB can effectively modulate both BCR/TLR9 and BCR/TLR7 endosomal-dependent activation of autoreactive B cells.

endogenous TLR ligands

Autorective B cells

inhibitory Fc receptor

Details

Title: Subtitle: FcγRIIB Regulation of BCR/TLR-Dependent Autoreactive B Cell Responses
Creators: Ana M Avalos - Department of Microbiology, Boston University School of Medicine, Boston, MA 02118
Melissa B Uccellini - Department of Microbiology, Boston University School of Medicine, Boston, MA 02118
Petar Lenert - Department of Internal Medicine, University of Iowa, Iowa City, IA 52242
Gregory A Viglianti - Department of Microbiology, Boston University School of Medicine, Boston, MA 02118
Ann Marshak-Rothstein - Department of Microbiology, Boston University School of Medicine, Boston, MA 02118
Resource Type: Journal article
Publication Details: European journal of immunology, Vol.40(10), pp.2692-2698
DOI: 10.1002/eji.200940184
PMID: 20809520
PMCID: PMC3060940
NLM abbreviation: Eur J Immunol
ISSN: 0014-2980
eISSN: 1521-4141
Language: English
Date published: 10/2010
Academic Unit: Immunology; Internal Medicine
Record Identifier: 9984094643102771

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