Multiple mutations in the variable region of the κ light chains of three monoclonal human IgM with anti-myelin-associated glycoprotein activity

• Published in: The Journal of biological chemistry 1989-12, Vol.264 (36), p.21481-21485
• Main Authors: Mihaesco, E, Ayadi, H, Congy, N, Gendron, M C, Roy, J P, Heyermann, H, Frangione, B, Brouet, J C
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Amino Acids - analysis; Antibodies, immunoglobulins; Antibodies, Monoclonal - genetics; Biological and medical sciences; Cyanogen Bromide; Epitopes - analysis; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Genes, Immunoglobulin; Humans; Immunoglobulin Fragments - isolation & purification; Immunoglobulin Heavy Chains - genetics; Immunoglobulin kappa-Chains - genetics; Immunoglobulin Light Chains - genetics; Immunoglobulin M - genetics; Immunoglobulin Variable Region - genetics; man; Molecular immunology; Molecular Sequence Data; Mutation; Myelin Proteins - immunology; Myelin-Associated Glycoprotein; Structure; Trypsin
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/S0021-9258(20)88209-X

Human monoclonal IgM having an antibody activity directed to myelin-associated glycoprotein have distinctive features. Amino-terminal sequence of light and heavy chains from 6 IgM κ that we have previously studied indicated that heavy chains belong to the VHIII subgroup, whereas light chains belong to 3 different subgroups of variability (VκI 2, VκII 1, and V κIV 3). We report here the complete sequence of the variable domain of 3 L chains: 2 V κIV and 1 V κII subgroups. Strikingly an unusually high degree of mutations clustered in the complementarity-determining regions (CDR) 1 and CDR 3 was found and the variable regions were joined to three different JK segments. Amino acid substitutions did not yield similar sequence in the CDRs suggesting that the κ chains had no predominant role in the unique binding activity of these IgM or alternatively they are directed against different epitopes. Data are consistent with the previously reported lack of easily demonstrated public idiotopes common to anti-myelin-associated glycoprotein IgM. The pathogenesis of these IgM autoantibodies is most likely different from that of previously studied monoclonal rheumatoid factors or cold agglutinins where a genetic restriction of L or H chains or both has been observed.