title: Generation of the antibody repertoire in individuals with multiple immunoglobulin heavy chain constant region gene deletions.
abstract: Antibodies against protein antigens are largely restricted to the IgG1 subclass in man, whereas anti-carbohydrate antibodies, at least in adults, are almost exclusively confined to the IgG2 subclass. In IgG2-deficient donors where the C gamma 2 gene is retained in the genome, antibodies against most polysaccharide antigens are absent. We therefore undertook a study of the antibody repertoire in 11 adult donors with immunoglobulin heavy chain constant region gene deletions, homozygous or heterozygous defects, encompassing the C gamma 2 gene. In all cases, antibodies against polysaccharide antigens were present and restricted to the remaining subclasses (IgG1 and/or IgG3). These results suggest an unrestricted use of the available VH gene repertoire in donors lacking the C gamma 2 gene, and imply that the limited antibody repertoire found in IgG2-deficient individuals with a retained C gamma 2 gene may be a consequence of an altered regulatory mechanism or a structural VH gene defect. However, furthermore, the deletion of multiple C gamma heavy chain constant region genes did not appear to decrease the IgG switch probability as such, since total serum levels of IgG appear to be normal.
mesh_terms: D000917:Antibody Formation; D000918:Antibody Specificity; D002872:Chromosome Deletion; D006801:Humans; D007127:Immunoglobulin Constant Regions / Q000235:genetics*; D007074:Immunoglobulin G / Q000032:analysis / Q000276:immunology; D007136:Immunoglobulins / Q000235:genetics*
chemical_list: D007127:Immunoglobulin Constant Regions; D007074:Immunoglobulin G; D007136:Immunoglobulins