Generation of the Antibody Repertoire in Individuals with Multiple Immunoglobulin Heavy Chain Constant Region Gene Deletions

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Abstract
Antibodies against protein antigens are largely restricted to the IgG1 cubclass in man, whereas anti‐carbohydrate antibodies, at least iin adult, are almost exclusively confined to the IgG2 subclass. In IgG2‐deficient donors where the Cγ2 gene is retained in the genome, antibodies against most polysaccharide antigens are absent. We therefore undertook a study of the antibody repretoire iin 11 adult donors withi immunoglobulin heavy chain constant region gene deletions, homozygous or heterozygous defects, encompassing the Cγ2 gene. In all cases, antibodies against polysccharide antigens were present and restricted to the remaining subclasses (IgG1 and/or IgG3). These results suggest and an unrestricted use of the available VH gene repertoire in donors lacking the Cγ2 gene, and imply that the limited antibody repertorie found in IgG2‐deficient individuals with a retained Cγ2 gene may be a consequence of an altered regulatory mechanism or a structural VH gene defect. However, furthermore, the delection of multiple Cγ2 heavy chain constant region genes did not appear to decrease the IgG switch probability as much, since total serum levels of IgG appear to be normal.