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Originally published In Press as doi:10.1074/jbc.M110109200 on December 3, 2001
J. Biol. Chem., Vol. 277, Issue 6, 4123-4127, February 8, 2002
Signal Transduction through the B Cell Antigen Receptor Is Normal
in Ataxia-Telangiectasia B Lymphocytes*
Peter
Speck §,
Masato
Ikeda¶,
Akiko
Ikeda,
Howard M.
Lederman **, and
Richard
Longnecker
From the Department of Microbiology-Immunology,
Northwestern University Medical School, Chicago, Illinois 60611, the
Endowood Division of Pediatric Immunology, Johns Hopkins
University School of Medicine, Baltimore, Maryland 21287, and the
§ Infectious Diseases Laboratories, Institute of Medical and
Veterinary Science, Frome Road,
Adelaide 5000, South Australia
The rare human genetic disorder
ataxia-telangiectasia (A-T) has multiple consequences including a
variable degree of immunodeficiency. Khanna and co-workers
(Khanna, K. K., Yan, J., Watters, D., Hobson, K., Beamish, H.,
Spring, K., Shiloh, Y., Gatti, R. A., and Lavin, M. F. (1997)
J. Biol. Chem. 272, 9489-9495) evaluated signaling in
Epstein-Barr virus (EBV) immortalized A-T lymphoblastoid cell lines
(LCLs), derived from the B cells of A-T patients. They showed that A-T
lymphoblastoid cells lack signaling through the B cell antigen receptor
and concluded that the fault in A-T encompasses intracellular signaling
in B cells. However, it is established that EBV latent membrane protein
2A (LMP2A) blocks signaling in EBV-bearing cells by interaction with
cellular tyrosine kinases. To test whether the reported fault in A-T B
cells was not inherent in A-T but the result of influence of wild-type
EBV, we derived A-T LCLs with wild-type or LMP2A-deleted EBV and
studied signaling in these cells in response to cross-linking the B
cell antigen receptor. We report that intracellular calcium
mobilization and tyrosine phosphorylation in LMP2A-depleted LCLs
derived from A-T patients is indistinguishable from that in
LMP2A-depleted LCLs derived from normal controls. Further, signaling is
blocked similarly in A-T and normal lymphoblastoid cells bearing
wild-type EBV. In conclusion there is no evidence of any defect in B
cell receptor signal transduction in A-T B cells.
*
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.
§
Supported by Grant 104880 from the National Health and Medical
Research Council of Australia.
¶
Special Fellow of the Leukemia and Lymphoma of America.
**
Supported by the A-T Children's Project (Deerfield, Florida), the
Pediatric General Clinical Research Center, the Johns Hopkins Hospital,
and Grant RR00052, Division of Research Resources, NICHD, National
Institutes of Health.
Stohlman Scholar of the Leukemia and Lymphoma Society of
America and supported by Public Health Service Grants CA62234 and CA73507 from the NCI and Grant DE13127 from the NIDCR, National Institutes of Health. To whom correspondence should be addressed: Dept.
of Microbiology-Immunology, Northwestern University Medical School,
Ward 6-231, 303 E. Chicago Ave., Chicago, IL 60611. Tel.: 312-503-0467; Fax: 312-503-1339; E-mail:
r-longnecker@northwestern.edu.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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Copyright © 2002 by the American Society for Biochemistry and Molecular Biology.
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