We have studied the antibody activity of humans myeloma proteins and macroglobulins for many years. These studies have related specificities to many determinants particularly carbohydrates which have never been obtained in mice. Furthermore the use of carbohydrate antigens whose structures are defined has allowed detailed analysis of the size, shape, and fine structure of their combining sites. Recently we have identified a macroglobulin of particular importance, IgMNOV, with specific to poly alpha (2->8)N-acetylneuraminic acid the capsular polysaccharide of the human pathogens, group B meningococci and E. coli K1. This antigen is a poor immunogen and no vaccine is available so that this anti-serum, cell lines of the same specificity, and the nucleotide and amino acid sequences are an invaluable resource in studying the potential for immuno-therapy. In addition, the antibody cross reacts with denatured DNA, the polynucleotides poly-A and poly-I, as well as N-CAM. The structural properties of the antibody which allow for these cross- reactivities, will be determined by comparing it with other monoclonal mouse antibodies specific for N-CAM, B meningococci, and DNA. These studies should lend fundamental insight into the molecular basis of antibody cross-reactivity as well as possibly permitting attempts at site-directed mutagenesis to eliminate these unwanted specificities, making the antibody safer and more effective for use in the treatment of human disease. We shall continue to explore and compare the repertoire of human monoclonal macroglobulins and myeloma proteins with repertoires in other species and with human-hybridomas. We shall also study the specificities of the monoclonal IgMs directed to the interior of the blood group substances in relation to their role as developmentally regulated antigens. We intend to follow the course of the benign monoclonal IgM specific for snail galactan to study its rises and falls since it appeared in 1978. We shall determine its VH and VL amino acid sequence as well the sequences of human monoclonal IgMs specific for chondroitin sulfates and Klebsiella K antigens, the group B antimeningococcal antibodies and those associated with motor neuron disease.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
Project #
Application #
Study Section
Allergy and Immunology Study Section (ALY)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Columbia University (N.Y.)
Schools of Medicine
New York
United States
Zip Code
Wu, A M; Wu, J H; Song, S C et al. (1996) Bandeiraea (Griffonia) simplicifolia lectin-I, isolectin A4, reacting with Tn (Ga1NAc alpha1 --> Ser/Thr) or galabiose (Ga1 alpha1 --> 4Ga1) containing ligands. FEBS Lett 398:183-6
Nickerson, K G; Tao, M H; Chen, H T et al. (1995) Human and mouse monoclonal antibodies to blood group A substance, which are nearly identical immunochemically, use radically different primary sequences. J Biol Chem 270:12457-65
Wu, A M; Song, S C; Wu, J H et al. (1995) Affinity of Bandeiraea (Griffonia) simplicifolia lectin-I, isolectin B4 for Gal alpha 1-->4 Gal ligand. Biochem Biophys Res Commun 216:814-20
Liao, J; Nickerson, K G; Bystricky, S et al. (1995) Characterization of a human monoclonal immunoglobulin M (IgM) antibody (IgMBEN) specific for Vi capsular polysaccharide of Salmonella typhi. Infect Immun 63:4429-32
Wu, T T; Johnson, G; Kabat, E A (1993) Length distribution of CDRH3 in antibodies. Proteins 16:1-7
Chen, J; Borden, P; Liao, J et al. (1992) Variable region cDNA sequences of three mouse monoclonal anti-idiotypic antibodies specific for anti-alpha(1----6)dextrans with groove- or cavity-type combining sites. Mol Immunol 29:1121-9
Wu, T T; Kabat, E A (1992) Possible use of similar framework region amino acid sequences between human and mouse immunoglobulins for humanizing mouse antibodies. Mol Immunol 29:1141-6
Padlan, E A; Kabat, E A (1991) Modeling of antibody combining sites. Methods Enzymol 203:3-21
Kabat, E A; Wu, T T (1991) Identical V region amino acid sequences and segments of sequences in antibodies of different specificities. Relative contributions of VH and VL genes, minigenes, and complementarity-determining regions to binding of antibody-combining sites. J Immunol 147:1709-19
Desai, R; Spatz, L; Matsuda, T et al. (1990) Molecular cloning of a human immunoglobulin heavy chain variable (VH) region with anti-myelin-associated glycoprotein activity. J Neuroimmunol 26:35-41