title: Signal transduction through the B cell antigen receptor is normal in ataxia-telangiectasia B lymphocytes.
abstract: 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.
authors.affiliation: Department of Microbiology-Immunology, Northwestern University Medical School, Chicago, Illinois 60611, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Speck
authors.forename: Masato
authors.initials: M
authors.lastname: Ikeda
authors.forename: Akiko
authors.initials: A
authors.lastname: Ikeda
authors.forename: Howard M
authors.initials: HM
authors.lastname: Lederman
authors.forename: Richard
authors.initials: R
authors.lastname: Longnecker
mesh_terms: D001260:Ataxia Telangiectasia / Q000097:blood / Q000378:metabolism*; D001402:B-Lymphocytes / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002461:Cell Line, Transformed; D006801:Humans; D007136:Immunoglobulins / Q000378:metabolism; D010766:Phosphorylation; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D015398:Signal Transduction; D014443:Tyrosine / Q000378:metabolism; D014763:Viral Matrix Proteins / Q000737:chemistry / Q000378:metabolism
chemical_list: C037662:EBV-associated membrane antigen, Epstein-Barr virus; D007136:Immunoglobulins; D011947:Receptors, Antigen, B-Cell; D014763:Viral Matrix Proteins; D014443:Tyrosine; D002118:Calcium