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Blood, 1 May 2007, Vol. 109, No. 9, pp. 3865-3872. Prepublished online as a Blood First Edition Paper on January 5, 2007; DOI 10.1182/blood-2006-09-046748.
Submitted September 12, 2006
Dept of Biochemistry, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway * Corresponding author; email: h.k.blomhoff{at}basalmed.uio.no.
Foreign CpG-DNA from viruses and bacteria can activate memory B cells through binding to toll-like receptor 9, and this pathway has been hypothesized to be involved in the continuous activation of memory B cells ensuring life-long humoral immunity. In this study we demonstrate that retinoic acid (RA) is a potent co-activator of this pathway in human B cells. RA enhanced the CpG-mediated proliferation of CD27+ memory B cells, and the proliferative response was accompanied by increased immunoglobulin (Ig) secretion indicative of plasma cell formation. The RA-induced proliferation was preceded by enhanced expression of cyclin D3, and both the expression of cyclin D3 and the induced Ig secretion was found to be dependent on IL-10. Importantly, RA increased the CpG-induced phosphorylation of ERK1/2, p38MAPK and I
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| Copyright © 2007 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||
B as early as 30 minutes after stimulation. By using specific inhibitors, all the RA-mediated events, including proliferation, cyclin D3 expression, IL-10 secretion, and Ig secretion were shown to be dependent on p38MAPK. Hence, we propose that RA can strengthen humoral immunity by promoting CpG-mediated stimulation of CD27+ B cells via activation of p38MAPK resulting in increased proliferation and differentiation to Ig-secreting plasma cells.
