Journal
TRENDS IN IMMUNOLOGY
Volume 23, Issue 2, Pages 75-80Publisher
ELSEVIER SCI LTD
DOI: 10.1016/S1471-4906(01)02115-9
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CD95(Apo-1/Fas) is crucial for the negative selection of B cells within the germinal center (GC). Impairment of CD95-mediated apoptosis results in defective affinity maturation and the persistence of autoreactive B-cell clones. CD95 was defined recently as a tumor-suppressor gene and is silenced in many tumor entities. In contrast to other malignancies, in GC-derived B-cell lymphomas, inactivation of the CD95 gene is often a result of deleterious mutations. Such mutations occur also at a low frequency in normal GC, but not naive, B cells. We propose that CD95mutations in B-cell lymphomas originate from the GC reaction and are introduced most probably as targeting errors of the somatic hypermutation machinery, which bears - besides its physiological role - an inherent risk of malignant transformation and the persistence of autoreactive B-cell specificities.
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