Genetic basis for the cross-reactive idiotypes on the light chains of human IgM anti-IgG autoantibodies

P. P. Chen, K. Albrandt, N. K. Orida, V. Radoux, R. Schrantz, Fu-Tong Liu, D. A. Carson

Research output: Contribution to journalArticlepeer-review

65 Scopus citations

Abstract

The role of immunoglobulin structural genes in the generation of autoantibodies in humans has not been elucidated. Human monoclonal IgM anti-IgG autoantibodies (rheumatoid factors, RFs) from unrelated people often share idiotypic antigens. Antibodies against synthetic peptides have localized two of the shared idiotypic determinants to the second and third complementarity-determining regions of the κ light chain. The reported sequences of several human RF light chains are remarkably homologous in these regions. Animal studies have shown that some shared idiotypic antigens represent serological markers for immunoglobulin variable (V)-region genes. Therefore, we hypothesized that human RF light chains derived from a single germ-line gene, designated V(κ)-(RF), or from a small family of very closely related genes. In the present experiments, we have isolated and sequenced two human V(κ) germ-line genes that encode κ light chains, which are identical or closely related to the light chains of human RF. The data indicate that the shared idiotypic antigens on RF are phenotypic markers for a κ V-region gene that is highly conserved in the human population. The results also imply that the light chains of IgM anti-IgG autoantibodies can be encoded by germ-line genes without any somatic mutation.

Original languageEnglish (US)
Pages (from-to)8318-8322
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume83
Issue number21
DOIs
StatePublished - 1986
Externally publishedYes

ASJC Scopus subject areas

  • Genetics
  • General

Fingerprint Dive into the research topics of 'Genetic basis for the cross-reactive idiotypes on the light chains of human IgM anti-IgG autoantibodies'. Together they form a unique fingerprint.

Cite this