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Originally published In Press as doi:10.1074/jbc.M201781200 on May 6, 2002

J. Biol. Chem., Vol. 277, Issue 32, 28830-28835, August 9, 2002
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CD45 Controls Interleukin-4-mediated IgE Class Switch Recombination in Human B Cells through Its Function as a Janus Kinase Phosphatase*

Takechiyo Yamada, Daocheng Zhu, Andrew Saxon, and Ke ZhangDagger

From the Hart and Louis Laboratory, Division of Clinical Immunology, Department of Medicine, UCLA School of Medicine, Los Angeles, California 90095-1680

CD45 plays a critical regulatory role in receptor signaling through its protein tyrosine phosphatase and Janus kinase (JAK) phosphatase activities. To investigate whether CD45 also plays a regulatory role in Ig class switching in human B cells, we examined the effects of CD45 triggering on Ig class switching to IgE and its relationship with CD45 JAK phosphatase activity. Anti-CD45 triggering of CD45 significantly inhibited interleukin-4 + anti-CD40-induced switch recombination in a switch recombination vector assay in stably transfected Ramos 2G6 human B cells, as well as Ig epsilon  germ-line transcription and Sµ-Sepsilon switch recombination in primary human B cells. These negative regulatory effects on Ig class switching were concomitant with the ability of CD45 to dephosphorylate the induced phosphorylation of JAK1, JAK3, and signal transducer and activator of transcription 6, but not on stress-activated/mitogen-activated protein kinases. We also showed that phosphorylated JAK1 and JAK3 were directly dephosphorylated by recombinant CD45 in vitro. These results indicate that CD45 is able to function as JAK phosphatase in human B cells and that this activity is directly associated with the negative regulation of the class switch recombination to IgE. CD45 may be an appropriate target drug for modulating IgE in allergic diseases.


* This work was supported by National Institutes of Health Grants AI-40551, AI-34567, AI-15251, AI-28697, and CA-16042 and an award from the Stein-Oppenheimer Foundation.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Dagger To whom correspondence should be addressed: Division of Clinical Immunology/Allergy, Dept. of Medicine, UCLA School of Medicine, 10833 Le Conte Ave., Los Angeles, CA 90095-1680. Tel.: 310-825-3699; Fax: 310-206-8107; E-mail: kzhang@mednet.ucla.edu.


Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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