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Trends Immunol. 2002 Feb;23(2):75-80.

The origin of CD95-gene mutations in B-cell lymphoma.

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Institut für Medizinische Mikrobiologie, Immunologie und Hygiene, Universität zu Köln, Germany.


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 CD95 mutations 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.

[Indexed for MEDLINE]

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