Generation of the antibody repertoire in individuals with multiple immunoglobulin heavy chain constant region gene deletions.

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.