Immunogenetic markers as probes for polymorphism, gene regulation and gene transfer in man--the Gm system in perspective.

The genetic markers of immunoglobulins (Ig) demonstrable by immunological methods have shown their usefulness as genetic probes. The study of these allotypes originally proved that Ig production is under conventional genetic control and also established that allelic exclusion is valid for the key molecules of the immune response. The codons responsible for the G1m(a) marker and their position in the human genome are precisely known. This knowledge implies that Gm typing may be used as a convenient and reliable means of following the fate of IgG constant gene segments. Anti-Gm's are common in rheumatoid arthritis. They appear early in the disease and may persist throughout life. The stimulus for their appearance has not yet been established. The anti-Gm's in the allegedly autoimmune disease rheumatoid arthritis are commonly and apparently paradoxically specific for Gm gene products of other persons. Another apparent paradox brought to light by Ig allotype research is the occasional appearance of non-nominal allotypes in contradiction to Mendelian laws. It is proposed that a plausible explanation for these two paradoxes is Ig gene transfer between individuals with viral vectors. Reasons for this proposal and some possible consequences of gene transfer in a polymorphic species are delineated. Immunogenetics and DNA technology in combination provide powerful tools to elucidate the fate of genes. A method allowing the assignment of G1m(a+) and G1m(a-) at the gene level by polymerase chain reaction analysis has recently been established and is briefly described.