Primary structure of the antigen-binding domains of a human oligodendrocyte-reactive IgM monoclonal antibody derived from a patient with multiple sclerosis.
Several murine IgM monoclonal antibodies (mAbs) promoting remyelination in mice were shown to be germline gene-encoded natural autoantibodies that react with oligodendrocytes and intracellular antigens. Here, we show that human oligodendrocyte-reactive IgM mAb DS1F8 derived from a patient with multiple sclerosis targets microtubule-like structures similar to the murine mAbs. Sequencing of the cDNAs of the variable regions revealed that the antigen-binding domains are also encoded by germline genes. These similarities of mAb DS1F8 to the murine mAbs promoting remyelination suggest that this human mAb is a natural autoantibody. This may imply that the engineering of human autoantibodies for therapy of demyelinating diseases is feasible.
Kirschning
E
E
Heinrich-Pette-Institute for Experimental Virology and Immunology at the University of Hamburg, Germany. kirschni@uke.uni-hamburg.de
Jensen
K
K
Dübel
S
S
Rutter
G
G
Hohenberg
H
H
Will
H
H
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D000937:Antigen-Antibody Reactions; D001323:Autoantibodies / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology* / Q000628:therapy; D001483:Base Sequence; D001666:Binding Sites, Antibody; D018076:DNA, Complementary / Q000235:genetics; D019084:Fluorescent Antibody Technique, Indirect; D015322:Gene Rearrangement, B-Lymphocyte; D005803:Genes, Immunoglobulin; D006367:HeLa Cells; D006801:Humans; D007075:Immunoglobulin M / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D007135:Immunoglobulin Variable Region / Q000235:genetics; D007167:Immunotherapy; D008969:Molecular Sequence Data; D009103:Multiple Sclerosis / Q000235:genetics / Q000276:immunology* / Q000628:therapy; D009186:Myelin Sheath / Q000276:immunology; D009836:Oligodendroglia / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016415:Sequence Alignment; D017385:Sequence Homology
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D018076:DNA, Complementary; D007075:Immunoglobulin M; D007135:Immunoglobulin Variable Region