Published ahead of print on January 24, 2005, doi:10.1165/rcmb.2004-0317OC Am. J. Respir. Cell Mol. Biol., Volume 32, Number 5, May 2005, 388-394 A more recent version of this article appeared on May 1, 2005
Submitted on October 7, 2004 B Lymphocyte Stimulator activates p38 MAPK in Human Ig Class Switch RecombinationTakechiyo Yamada1*,1 Division Clinical Immunology, Department of Medicine, University of California at Los Angeles School of Medicine, Los Angeles, USA; Department of Otorhinolaryngology, University of Fukui, Yoshida, Fukui, Japan, 2 Division Clinical Immunology, Department of Medicine, University of California at Los Angeles School of Medicine, Los Angeles, USA * To whom correspondence should be addressed. E-mail: ymdtkcy{at}fmsrsa.fukui-med.ac.jp.
B lymphocyte stimulator (BLyS), a member of the tumor necrosis factor ligand superfamily has potent costimulatory activity on B cells. To investigate BLyS-signaling in Ig class switching, we examined whether BLyS could control stress-activated protein kinases in human B cells as well as whether BLyS could induce human Ig class switch recombination (CSR) and expression of activation-induced cytidine deaminase (AID). BLyS induced the phosphorylation p38 mitogen-activated protein kinase (p38 MAPK) and c-Jun N-terminal kinase (JNK) in human B cells. As evidence of Ig class switch, BLyS plus IL-4 induced generation of switch circle transcripts (CTs) to gamma 1-2, gamma 4 and epsilon while BLyS plus IL-10 induced gamma 1-2 CTs only. BLyS strongly induced AID-expression in the presence of IL-4. Treatment with SB203580, specific inhibitor of p38 MAPK signaling, almost completely reversed BLyS-induced CSR and AID-expression in human B cells. The switch vector assay also showed that BLyS induced CSR in the presence of IL-4 in Ramos 2G6 human B cells and SB203580 reversed CSR. These results indicate that BLyS-activated p38 MAPK plays an essential role in BLyS-induced AIDexpression and CSR in human B cells.
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