Massimo Morra, Robert A Barrington, Ana C Abadia-Molina, Susumo Okamoto, Aimee Julien, Charles Gullo, Anuj Kalsy, Matthew J Edwards, Gang Chen, Rosanne Spolski, Warren J Leonard, Brigitte T Huber, Persephone Borrow, Christine A Biron, Abhay R Satoskar, Michael C Carroll, Cox Terhorst
More than half of patients with X-linked lympho-proliferative disease, which is caused by a defect in the intracellular adapter protein SH2D1A, suffer from an extreme susceptibility to Epstein-Barr virus. One-third of these patients, however, develop dysgammaglobulenemia without an episode of severe mononucleosis. Here we show that in SH2D1A(-/-) mice, both primary and secondary responses of all Ig subclasses are severely impaired in response to specific antigens. Because germinal centers were absent in SH2D1A(-/-) mice upon primary immunization, and because SH2D1A was detectable in wt germinal center B cells, we examined whether SH2D1A(-/-) B cell functions were impaired...
March 29, 2005: Proceedings of the National Academy of Sciences of the United States of America