Glucocorticoid inhibition of activation-induced cytidine deaminase expression in human B lymphocytes

MOLECULAR AND CELLULAR ENDOCRINOLOGY

卷:382

Article

Benko, Ann L.¹  Olsen, Nancy J.²  Kovacs, William J.¹ 

[1] Penn State Univ, Coll Med, Div Endocrinol Diabet & Metab, Milton S Hershey Med Ctr, Hershey, PA 17033 USA

[2] Penn State Univ, Coll Med, Milton S Hershey Med Ctr, Div Rheumatol, Hershey, PA 17033 USA

关键词: Glucocorticoids;    B Lymphocytes;    Activation-induced cytidine deaminase;    Class switch recombination;    Somatic hypermutation;   

DOI  :  10.1016/j.mce.2013.11.001

来源: Elsevier

【 摘 要 】

We examined whether glucocorticoids could modulate the expression of activation-induced cytidine deaminase (AICDA), the principal regulator of the processes of immunoglobulin gene somatic hypermutation and class switch recombination in B lymphocytes. Treatment of human B cells with IL-4 and anti-CD40 antibody for 18-20 h resulted in induction of expression of AICDA mRNA by over 10-fold. Dexamethasone at 10 nM concentration inhibited AICDA induction by an average of 51.8% (p <0.0001). These effects of glucocorticoids were found to be dose dependent in the physiologic range and were reversible by co-treatment with a glucocorticoid receptor antagonist. Human B cell viability and proliferation were unaltered by glucocorticoid treatment. These data demonstrate that physiologic concentrations of glucocorticoids can act on human B lymphocytes through glucocorticoid receptor-mediated mechanisms to diminish the expression of AICDA, a key regulator of humoral immune responses. (C) 2013 Elsevier Ireland Ltd. All rights reserved.

【 授权许可】

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