Studies on the Nature of the Abnormality of B Cell Differentiation in Avian Lymphoid Leukosis: Production of Heterogeneous IgM by Tumor Cells

In chickens with lymphoid leukosis, immunoglobulin production, the distribution of immunoglobulin in tumor cells, the morphology of tumor cells, and the distribution of viruses were examined. Regardless of their location, virtually all of the lymphoma cells had detectable surface IgM; the prevalent distribution pattern produced by the bivalent fluorescein-labeled antibodies to IgM determinants was one of global patching. Variable amounts of cytoplasmic IgM were often detected in tumor cells. Release of IgM from tumor cells was indicated by the finding of high levels of serum IgM in birds with widespread lymphomas. Both high molecular weight and low molecular weight IgM were present in serum from tumorous birds, and both forms were electrophoretically heterogeneous. Lymphomatous birds had elevated titers of agglutinating antibodies to sheep and human erythrocytes but had normal levels of antibodies to Salmonella typhi flagellar antigens and leukosis virus neutralizing antibodies. None of the tumor cells contained or carried on their surface IgG or IgA heavy chain determinants; IgG levels were normal in tumor-bearing birds, but IgA levels were usually elevated. Multiple bursal follicles were involved by the tumor process. The tumor nodules in the bursa and in other organs of individual birds often differed in the size, cytoplasmic RNA content, and amount of cytoplasmic IgM that were characteristic of their constituent cells. Most of the tumor cells appeared not to achieve normal maturation; mature plasma cells were usually sparsely distributed around tumor nodules. The tumor cells were found by electron microscopy to contain an abundance of cytoplasmic ribosomes in clusters and scattered strands of rough endoplasmic reticulum. Virus particles budding from cell membranes of tumor cells were occasionally seen, but cell-associated viruses were much more abundant in a variety of non-tumorous cell types. These observations are interpreted to suggest that the avian leukosis viruses exert their lymphomagenic effect by interrupting the switch from IgM to IgG gene expression that normally occurs within clones of bursal lymphocytes.