The Journal of Experimental Medicine
Janeway's Immunobiology 7th Edition
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Published online 18 April 2000.
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© The Rockefeller University Press, 0022-1007/2000/4/1319/ $5.00
The Journal of Experimental Medicine, Volume 191, Number 8, April 17, 2000 1319-1332

Original Article

A Novel B Lymphocyte–associated Adaptor Protein, Bam32, Regulates Antigen Receptor Signaling Downstream of Phosphatidylinositol 3-Kinase

Aaron J. Marshalla, Hiroaki Niiroa, Cara G. Lernerb, Theodore J. Yunb, Sushma Thomasc, Christine M. Distechec, and Edward A. Clarka,b,d
a Department of Microbiology, University of Washington, Seattle, Washington 98195
b Department of Immunology, University of Washington, Seattle, Washington 98195
c Department of Pathology, University of Washington, Seattle, Washington 98195
d Regional Primate Research Center, University of Washington, Seattle, Washington 98195

Correspondence to: Aaron J. Marshall, Department of Microbiology, University of Washington, Seattle, WA 98195. Tel:206-543-7414 Fax:206-543-8297 E-mail:aaronn{at}u.washington.edu.

We have identified and characterized a novel src homology 2 (SH2) and pleckstrin homology (PH) domain–containing adaptor protein, designated Bam32 (for B cell adaptor molecule of 32 kD). cDNAs encoding the human and mouse Bam32 coding sequences were isolated and the human bam32 gene was mapped to chromosome 4q25–q27. Bam32 is expressed by B lymphocytes, but not T lymphocytes or nonhematopoietic cells. Human germinal center B cells show increased Bam32 expression, and resting B cells rapidly upregulate expression of Bam32 after ligation of CD40, but not immunoglobulin M. Bam32 is tyrosine-phosphorylated upon B cell antigen receptor (BCR) ligation or pervanadate stimulation and associates with phospholipase C{gamma}2. After BCR ligation, Bam32 is recruited to the plasma membrane through its PH domain. Membrane recruitment requires phosphatidylinositol 3-kinase (PI3K) activity and an intact PI(3,4,5)P3-binding motif, suggesting that membrane association occurs through binding to 3-phosphoinositides. Expression of Bam32 in B cells leads to a dose-dependent inhibition of BCR-induced activation of nuclear factor of activated T cells (NF-AT), which is blocked by deletion of the PH domain or mutation of the PI(3,4,5)P3-binding motif. Thus, Bam32 represents a novel B cell–associated adaptor that regulates BCR signaling downstream of PI3K.

Key Words: immunoglobulin, germinal center, signal transduction, SH2 domain, pleckstrin homology domain


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