Glucocorticoid inhibition of activation-induced cytidine deaminase expression in human B lymphocytes
Ann L Benko1, Nancy J Olsen2, William J Kovacs1
1Division of Endocrinology, Diabetes, and Metabolism, The Pennsylvania State University, College of Medicine, Milton S. Hershey Medical Center, Hershey, PA 17033, United States.
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.
More Related Videos
08:49Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries
Published on: January 22, 2019
14:18Author Spotlight: Investigating the Potential of Chinese Herbal Medicinal Active Dioscin in Treating IgA Nephropathy
Published on: October 13, 2023
Related Concept Videos
Drugs for Treatment of Crohn's Disease in IBD Using Glucocorticoids
B Cell Activation and Differentiation
When naive B cells encounter a specific antigen that can bind to the B cell receptor (BCR) on their surface, they undergo sensitization to respond to the antigen's presence. Sensitization begins with...
Antiasthma Drugs: Inhaled Corticosteroids and Glucocorticoids
ICS work through a multifaceted mechanism of action. They suppress the inflammatory response caused by the proliferation of TH cells. They also reduce the transcription of the IL-2 gene, which is involved in the...
Drugs for Treatment of Crohn's Disease in IBD Using Immunomodulatory Agents
Inhibition of Cdk Activity
