Journal
CLINICAL IMMUNOLOGY
Volume 201, Issue -, Pages 70-78Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.clim.2019.02.009
Keywords
B cell; Gene regulation; Antibodies; Human; Toll like receptors; Adrenocorticotropin
Categories
Funding
- Pennsylvania Department of Health using Tobacco Settlement Funds
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We sought evidence for direct effects of repository corticotropin (RCI; an FDA-approved treatment for selected cases of SLE) on isolated human B lymphocytes activated by engagement of TLR9 and B cell receptors. ODN 2395/algM treatment was found to result in induction of 162 distinct mRNAs and suppression of 80 mRNAs at 24 h. RCI treatment resulted in suppression of 14 of the ODN 2395/alpha IgM-induced mRNAs (mean suppression to 23.6 +/- 3.1% of stimulated value). The RCI-suppressed mRNAs included two critical regulators of class switch recombination, AICDA and BATF. RCI treatment also resulted in induction of 5 of the ODN 2395/alpha IgM-suppressed mRNAs (mean induction by RCI = 7.65 +/- 2.34-fold). The RCI-induced mRNAs included SLAMF3, a cell surface receptor capable of inhibiting autoantibody responses. These studies reveal that RCI treatment of human B cells reverses key elements of the early mRNA response to TLR9 and B cell receptor engagement.
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