Autosomal Hyper-IgM Syndromes Caused by an Intrinsic B Cell Defect

Abstract

Abstract The study of inherited hyper-IgM syndromes (HIGM) has greatly contributed to our understanding of the normal processes of antibody maturation, because these syndromes have in common a defect in immunoglobulin (Ig) class switch recombination (CSR), as demonstrated by normal or elevated serum IgM levels. This is in contrast to absent or strongly decreased levels of the other immunoglobulin (Ig) isotypes. Antibody maturation leads to the production of antibodies of different isotypes and formation of B cell receptors (BCR) with high affinity for antigen. This event usually takes place in the secondary lymphoid organs (spleen, lymph nodes, tonsils) in an antigenand T lymphocyte–dependent manner. When mature (but still naive) IgM+ IgD+ B cells, after emigrating from the bone marrow (or fetal liver), encounter an antigen that is specifically recognized by their BCR, they proliferate vigorously and give birth to a unique lymphoid formation, the germinal center. In this location, B cells undergo the two major events of maturation: CSR and somatic hypermutation (SHM).