Immunoglobulin class-switch recombination deficiencies.
Immunoglobulin class-switch recombination deficiencies (Ig-CSR-Ds) are rare primary immunodeficiencies characterized by defective switched isotype (IgG/IgA/IgE) production. Depending on the molecular defect in question, the Ig-CSR-D may be combined with an impairment in somatic hypermutation (SHM). Some of the mechanisms underlying Ig-CSR and SHM have been described by studying natural mutants in humans. This approach has revealed that T cell-B cell interaction (resulting in CD40-mediated signaling), intrinsic B-cell mechanisms (activation-induced cytidine deaminase-induced DNA damage), and complex DNA repair machineries (including uracil-N-glycosylase and mismatch repair pathways) are all involved in class-switch recombination and SHM. However, several of the mechanisms required for full antibody maturation have yet to be defined. Elucidation of the molecular defects underlying the diverse set of Ig-CSR-Ds is essential for understanding Ig diversification and has prompted better definition of the clinical spectrum of diseases and the development of increasingly accurate diagnostic and therapeutic approaches.
Anne
A
Durandy
Sven
S
Kracker
D000818:Animals; D006801:Humans; D017578:Immunoglobulin Class Switching / Q000235:genetics / Q000276:immunology*; D007075:Immunoglobulin M / Q000235:genetics / Q000276:immunology; D007153:Immunologic Deficiency Syndromes / Q000175:diagnosis / Q000235:genetics / Q000276:immunology*; D011995:Recombination, Genetic / Q000235:genetics / Q000276:immunology*
D007075:Immunoglobulin M