No influence of conversions affecting allotype expression on the IgG subclass restriction of specific antibodies

Antibodies against any given antigen are usually restricted to a particular class or subclass, a finding which has been suggested to be due to a preferential association between particular VH and CH genes. The DNA sequences regulating this process are as yet entirely unknown. It is likely however that some of these regulatory sequences are located within or in the immediate vicinity of the immunoglobulin genes themselves. We therefore analyzed the IgG subclass pattern of specific antibodies in sera from individuals displaying mutations, duplications, deletions or gene conversions event (replacing parts of the constant region genes of one subclass with that of another) affecting the allotype expression of immunoglobulin heavy chain constant region genes. Marked influences on antibody levels were noted in sera from individuals displaying duplication or deletions of constant region genes. However, in no case of gene conversion or mutation was there any measurable influence on the antibody pattern, clearly suggesting a lack of VH gene regulation by sequences within and possibly also immediately downstream of the constant region genes.