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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. This Article Full Text (PDF) Erratum (v110,p4233) All Versions of this Article: blood-2006-09-046748v1 109/9/3865    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Ertesvag, A. Articles by Blomhoff, H. K. Search for Related Content PubMed PubMed Citation Articles by Ertesvag, A. Articles by Blomhoff, H. K. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted September 12, 2006 Accepted December 14, 2006 Vitamin A potentiates CpG-mediated memory B cell proliferation and differentiation: Involvement of early activation of p38MAPK Aase Ertesvag, Hans-Christian Aasheim, Soheil Naderi, and Heidi Kiil Blomhoff* Dept of Biochemistry, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway Dept of Immunology, Rikshospitalet-Radiumhospitalet, 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 IB 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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: T. M. Garcia-Bates, C. J. Baglole, M. P. Bernard, T. I. Murant, P. J. Simpson-Haidaris, and R. P. Phipps Peroxisome Proliferator-Activated Receptor {gamma} Ligands Enhance Human B Cell Antibody Production and Differentiation J. Immunol., December 1, 2009; 183(11): 6903 - 6912. [Abstract] [Full Text] [PDF] Y. Ma and A. C. Ross Toll-Like Receptor 3 Ligand and Retinoic Acid Enhance Germinal Center Formation and Increase the Tetanus Toxoid Vaccine Response Clin. Vaccine Immunol., October 1, 2009; 16(10): 1476 - 1484. [Abstract] [Full Text] [PDF] F. Capolunghi, S. Cascioli, E. Giorda, M. M. Rosado, A. Plebani, C. Auriti, G. Seganti, R. Zuntini, S. Ferrari, M. Cagliuso, et al. CpG Drives Human Transitional B Cells to Terminal Differentiation and Production of Natural Antibodies J. Immunol., January 15, 2008; 180(2): 800 - 808. [Abstract] [Full Text] [PDF]

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