On the origin of antibodies to immunoglobulin genetic markers in rheumatoid arthritis. An outline of a novel concept of the nature of rheumatoid arthritis--transduction in man.

Anti-Gm's in rheumatoid arthritis patients detect products of the Mendelian genes G1ma, G1mx, G3mb, G3mc, G3mg, G3mst. Commonly, these anti-Gm's are specific for other individuals immunoglobulin allotypes. Reasons are given for the contention that such anti-Gm's in patients with rheumatoid arthritis are indicative of the expression of nonnominal allotypes, the genes for which have been transferred from one individual to another by means of a B cell virus. This process - akin to transduction and occurring after the tolerance induction period - may lead to a chimaeric state of the B cell compartment in rheumatoid arthritis patients. Special features of Ig gene regulation in normal B cell progression are allelic exclusion and the excision-expulsion-rejoining of DNA segments. Perturbation of B cell regulation by external genomes may be favoured by allelic exclusion. The DNA excision-rejoining processes may have consequences for concomitant (viral) nucleic acid assembly, particularly for viruses sharing nucleotide sequences with the Ig switch regions.