SERUM IMMUNOGLOBULIN LEVELS IN HETEROZYGOUS SUBJECTS WITH IMMUNOGLOBULIN HEAVY-CHAIN CONSTANT-REGION GENE DELETIONS

The immunoglobulin heavy chain constant region locus is a multigene fa mily composed of nine genes and two pseudogenes, whose high homology i s often responsible for meiotic mispairings leading to deleted and dup licated haplotypes. These rearrangements have a population frequency o f about 1.5% and 4.5% respectively, with a significant difference betw een deletions and duplications (P < 0.001). Both positive selection of duplications or negative selection against deletions can account for this imbalance. Serum levels of IgG and IgA subclasses, of IgE, of iso hemagglutinins and of IgG antibodies to tetanus toroid and pneumococca l antigens were evaluated in 11 heterozygous carriers of constant regi on deletions. There was no gross abnormality in serum IgG and IgA subc lass levels, with the possible exception of G1-deleted individuals; fu rthermore, isohemagglutinins and anti-tetanus toroid and pneumococcal IgG antibodies are in the normal range, suggesting that the humoral im mune response is normal in these carriers. The influence of single and multiple immunoglobulin heavy chain constant region gene deletions on the humoral response is discussed.