A human monoclonal macroglobulin with specificity for alpha(2----8)-linked poly-N-acetyl neuraminic acid, the capsular polysaccharide of group B meningococci and Escherichia coli K1, which crossreacts with polynucleotides and with denatured DNA.
We have described an IgM antibody from a patient with macroglobulinemia specifically reacting with poly-alpha(2----8)N-acetyl neuraminic acid (NeuNAc) the capsular polysaccharide of two important human pathogens, group B meningococcus and E. coli K1. This antibody has a narrowly defined specificity in its interactions with polysaccharides, being unable to bind poly-alpha(2----9)NeuNAc or alternating poly-alpha(2----8)alpha(2----9)NeuNAc. However, it shows interesting crossreactivity with seemingly unrelated polynucleotides and denatured DNA, supporting the hypothesis that charged groups with a given spacing may determine the specificity of antigen-antibody interactions on otherwise dissimilar molecular structures. Despite the crossreactivity with denatured DNA and polynucleotides, the antibody does not appear to have adverse effects in the patient. The antibody protects newborn rats against E. coli K1 infection, as well as the standard horse antiserum H46, and one would expect it to prove useful in humans as an adjunct to antibiotic therapy in infections with group B meningococcus and E. coli K1. We have attempted to clone the antibody-producing cells from peripheral blood, and have shown that the relevant cells are present and can be cultured.
D000368:Aged; D000818:Animals; D000911:Antibodies, Monoclonal / Q000032:analysis*; D000918:Antibody Specificity; D000942:Antigens, Bacterial; D001402:B-Lymphocytes / Q000276:immunology; D016667:Bacterial Capsules; D001666:Binding Sites, Antibody; D002999:Clone Cells / Q000276:immunology; D003429:Cross Reactions; D004247:DNA / Q000276:immunology* / Q000378:metabolism; D004926:Escherichia coli / Q000276:immunology; D006801:Humans; D007075:Immunoglobulin M / Q000378:metabolism / Q000627:therapeutic use; D008259:Macroglobulins / Q000032:analysis*; D008297:Male; D019158:N-Acetylneuraminic Acid; D009345:Neisseria meningitidis / Q000276:immunology; D011119:Polynucleotides / Q000276:immunology*; D011135:Polysaccharides, Bacterial / Q000276:immunology*; D011233:Precipitin Tests; D051381:Rats; D011919:Rats, Inbred Strains; D012794:Sialic Acids / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial; D007075:Immunoglobulin M; D008259:Macroglobulins; D011119:Polynucleotides; D011135:Polysaccharides, Bacterial; D012794:Sialic Acids; C036962:capsular polysaccharide K1; C039455:capsular polysaccharide, meningococcal group B; D004247:DNA; D019158:N-Acetylneuraminic Acid