Format

Send to

Choose Destination
Mol Immunol. 2014 Dec;62(2):321-8. doi: 10.1016/j.molimm.2014.01.003. Epub 2014 Feb 6.

NFATc2 (NFAT1) assists BCR-mediated anergy in anti-insulin B cells.

Author information

1
Division of Rheumatology and Immunology, Department of Medicine, Vanderbilt University, MCN T3113, 21st Avenue S., Nashville, TN 37232, USA.
2
Division of Rheumatology and Immunology, Department of Medicine, Vanderbilt University, MCN T3113, 21st Avenue S., Nashville, TN 37232, USA; Department of Pathology, Microbiology, and Immunology, Vanderbilt University, MCN T3113, 21st Avenue S., Nashville, TN 37232, USA. Electronic address: james.w.thomas@vanderbilt.edu.
3
Department of Pathology, Microbiology, and Immunology, Vanderbilt University, MCN T3113, 21st Avenue S., Nashville, TN 37232, USA; Division of Allergy, Pulmonary, and Critical Care, Department of Medicine, Vanderbilt University, MCN T3113, 21st Avenue S., Nashville, TN 37232, USA.

Abstract

NFAT transcription factors play critical roles in both the activation and repression of T and B lymphocyte responses. To understand the role of NFATc2 (NFAT1) in the maintenance of tolerance for anti-insulin B cells, functionally inactive NFATc2 (NFATc2(-/-)) was introduced into C57BL/6 mice that harbor anergic anti-insulin 125Tg B cells. The production and peripheral maturation of anti-insulin B cells into follicular and marginal zone subsets was not altered by the absence of functional NFATc2. Surface B cell receptor expression levels, important for tonic signaling and altered by anergy, were not altered in any spleen B cell subset. The levels of anti-insulin antibodies were not different in 125Tg/B6/NFATc2(-/-) mice and the anti-insulin response remained silenced following T cell dependent immunization. However, studies addressing in vitro proliferation reveal the anergic state of 125Tg B cells is relieved in 125Tg/B6/NFATc2(-/-) B cells in response to BCR stimulation. In contrast, anergy is not released in 125Tg/B6/NFATc2(-/-) B cells following stimulation with anti-CD40. The relief of anergy to BCR stimulation in 125Tg/B6/NFATc2(-/-) B cells is associated with increased transcription of both NFATc1 and NFATc3 while expression of these NFATs does not change in anti-IgM stimulated 125Tg/B6/NFATc2(+/+) B cells. The data suggest that NFATc2 plays a subtle and selective role in maintaining anergy for BCR stimulation by repressing the transcription of other NFAT family members.

KEYWORDS:

Autoimmunity; B cell; Insulin; NFAT; Signaling; Tolerance

PMID:
24507801
PMCID:
PMC4125564
DOI:
10.1016/j.molimm.2014.01.003
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center