Immunoglobulin Class-Switch Recombination Defects

Abstract

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