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.
