This Article Full Text Full Text (PDF) All Versions of this Article: 2004-0317OCv1 32/5/388    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Yamada, T. Articles by Saxon, A. Search for Related Content PubMed PubMed Citation Articles by Yamada, T. Articles by Saxon, A.

B Lymphocyte Stimulator Activates p38 Mitogen-Activated Protein Kinase in Human Ig Class Switch Recombination

Hart and Louis Laboratory, Division of Clinical Immunology, Department of Medicine, UCLA School of Medicine, Los Angeles, California; and Department of Otorhinolaryngology, University of Fukui, Fukui, Japan

Correspondence and requests for reprints should be addressed to Takechiyo Yamada, Division of Clinical Immunology, Department of Medicine, UCLA School of Medicine, 10833 Le Conte Ave, Los Angeles, CA 90095-1680. 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 interleukin (IL)-4 induced generation of switch circle transcripts (CTs) to 1–2, 4, and epsilon, whereas BLyS plus IL-10 induced 1–2 CTs only. BLyS strongly induced AID expression in the presence of IL-4. Treatment with SB203580, a 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 that SB203580 reversed CSR. These results indicate that BLyS-activated p38 MAPK plays an essential role in BLyS-induced AID-expression and CSR in human B cells.

Key Words: B lymphocytes • BLyS • Ig isotype switching • p38 MAPK

This article has been cited by other articles:

				W. Stohl, N. Jacob, W. J. Quinn III, M. P. Cancro, H. Gao, C. Putterman, X. Gao, L. Pricop, and M. N. Koss Global T Cell Dysregulation in Non-Autoimmune-Prone Mice Promotes Rapid Development of BAFF-Independent, Systemic Lupus Erythematosus-Like Autoimmunity J. Immunol., July 1, 2008; 181(1): 833 - 841. [Abstract] [Full Text] [PDF]

				H.-A Kim, S.-H. Jeon, G.-Y. Seo, J.-B. Park, and P.-H. Kim TGF-{beta}1 and IFN-{gamma} stimulate mouse macrophages to express BAFF via different signaling pathways J. Leukoc. Biol., June 1, 2008; 83(6): 1431 - 1439. [Abstract] [Full Text] [PDF]

				D. Frasca, A. M. Landin, R. L. Riley, and B. B. Blomberg Mechanisms for Decreased Function of B Cells in Aged Mice and Humans J. Immunol., March 1, 2008; 180(5): 2741 - 2746. [Abstract] [Full Text] [PDF]

				C. O. Jacob, L. Pricop, C. Putterman, M. N. Koss, Y. Liu, M. Kollaros, S. A. Bixler, C. M. Ambrose, M. L. Scott, and W. Stohl Paucity of Clinical Disease despite Serological Autoimmunity and Kidney Pathology in Lupus-Prone New Zealand Mixed 2328 Mice Deficient in BAFF J. Immunol., August 15, 2006; 177(4): 2671 - 2680. [Abstract] [Full Text] [PDF]