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.
Grubb
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R
Department of Medical Microbiology, University of Lund, Sweden.
Kjellen
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D000888:Antibodies, Anti-Idiotypic / Q000235:genetics*; D001172:Arthritis, Rheumatoid / Q000209:etiology / Q000235:genetics / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D005786:Gene Expression Regulation; D005819:Genetic Markers; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000472:pathogenicity; D006801:Humans; D007129:Immunoglobulin Gm Allotypes / Q000235:genetics; D014161:Transduction, Genetic
D000888:Antibodies, Anti-Idiotypic; D005819:Genetic Markers; D007129:Immunoglobulin Gm Allotypes