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

Bonami RH, Wolfle WT, Thomas JW, Kendall PL
Mol Immunol. 2014 62 (2): 321-8

PMID: 24507801 · PMCID: PMC4125564 · DOI:10.1016/j.molimm.2014.01.003

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.

MeSH Terms (12)

Animals B-Lymphocyte Subsets Cells, Cultured Immune Tolerance Insulin Insulin Antibodies Mice Mice, Inbred C57BL NFATC Transcription Factors Receptors, Antigen, B-Cell T-Lymphocytes Transcription, Genetic

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