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

Author:
Benko, Ann L., Olsen, Nancy J., Kovacs, William J.
Source:
Molecular and Cellular Endocrinology 2014 v.382 pp. 881-887
ISSN:
0303-7207
Subject:
B-lymphocytes, antagonists, antibodies, cell viability, cytidine deaminase, dexamethasone, dose response, glucocorticoid receptors, glucocorticoids, humans, humoral immunity, immunoglobulin genes, interleukin-4, messenger RNA
Abstract:
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 18–20h resulted in induction of expression of AICDA mRNA by over 10-fold. Dexamethasone at 10nM 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.
Agid:
5522546