Human IgM monoclonal proteins that bind 3-fucosyllactosamine, asialo-GM1, and GM1.
Analysis of monoclonal human Ig that occur in association with lymphoproliferative diseases has provided valuable information about antibody structure and idiotypes. We analyzed 940 human sera that contained monoclonal IgM proteins for their ability to bind to four carbohydrate epitopes. Ten sera bound asialo-GM1, five of these sera also bound GM1, 10 bound to 3-fucosyllactosamine (3-FL), and one each bound to levan and galactan. Although the antibody activity in each serum was associated with a single L chain isotype, both kappa and lambda isotypes were represented among the proteins that bound to asialo-GM1 and to 3-FL. Some antibodies against asialo-GM1 were highly specific for this compound, whereas others cross-reacted with the structurally related gangliosides GM1 and GD1b. The antibodies to asialo-GM1 also varied considerably in their ability to lyse liposomes that contain asialo GM1. An association of IgM mAb against gangliosides with peripheral neuropathies has been reported recently, but only one of five patients whose antibodies reacted with GM1 ganglioside had a neuropathy. The antibodies that bound 3-FL exhibited narrower specificity, and less than 10% cross reactivity was noted with structurally related carbohydrates. The frequency of monoclonal proteins that bound 3-FL and asialo-GM1, approximately 1:100 sera for each specificity, was surprisingly high in view of the fact that both of these epitopes are expressed in human tissues. We suggest that these antibodies may be poly-specific and/or that the subset of B lymphocytes that synthesizes these anti-carbohydrate antibodies undergoes malignant transformation more frequently than other B lymphocytes.
Marcus
D M
DM
Department of Medicine, Baylor College of Medicine, Houston, TX 77030.
Perry
L
L
Gilbert
S
S
Preud'homme
J L
JL
Kyle
R
R
D000911:Antibodies, Monoclonal / Q000276:immunology; D000918:Antibody Specificity; D005677:G(M1) Ganglioside / Q000276:immunology*; D006017:Glycolipids / Q000276:immunology*; D006028:Glycosphingolipids / Q000276:immunology*; D007075:Immunoglobulin M / Q000276:immunology*; D016256:Lewis X Antigen; D008232:Lymphoproliferative Disorders / Q000276:immunology; D009844:Oligosaccharides / Q000276:immunology; D010265:Paraproteinemias / Q000276:immunology*
D000911:Antibodies, Monoclonal; D006017:Glycolipids; D006028:Glycosphingolipids; D007075:Immunoglobulin M; D016256:Lewis X Antigen; D009844:Oligosaccharides; D005677:G(M1) Ganglioside; C018835:asialo GM1 ganglioside