Maturation of the secondary antibody repertoire is generated by means of class switch recombination and somatic hypermutation. The molecular mechanisms underlying these important processes have long remained obscure. Inherited defects in class switch recombination variably associated to defects in somatic hypermutation are a group of genetically heterogeneous diseases, the characterization of which has allowed recognition that T-B cell interaction (resulting in CD40-mediated signaling), intrinsic B cell mechanisms, and complex DNA repair machinery are involved in class switch recombination and somatic hypermutation. Elucidation of the molecular defects underlying these disorders has been essential to better understand the molecular basis of immunoglobulin diversification and has offered the opportunity to define the clinical spectrum of these diseases and to prompt more accurate diagnostic and therapeutic approaches.
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