The overall goal of this project is to promote a clearer understanding of the mechanisms of hematopoietic cell differentiation by characterizing cell surface antigens expressed during the development, and after the maturation, of the blood elements. We have primarily focused on the characterization of a novel antigen identified by a monoclonal antibody LIP-6. LIP-6 was produced against an undifferentiated murine hematopoietic cell line in order to identify antigens expressed early in development. The LIP-6 antigen is composed of three disulphide-linked proteins that are expressed by bone marrow cells, B lineage cells and macrophages but absent on all T lineage cells. Antibodies to LIP-6 can induce proliferation of mature B cells in the absence of T cells, suggesting that LIP-6 may be important in activation of mature B cells. A population of bone marrow cells, identified by its expression of LIP-6, has been found to be an immature progenitor population with limited differentiation capacity within the B, T and myeloid cell lineages. Future studies will attempt to isolate the gene coding for the LIP-6 protein and further characterize the population of cells expressing LIP-6 in bone marrow. These studies will hopefully yield new information about the cellular interactions important in B development and B lymphocyte interactions. Two other cell surface antigens expressed on bone marrow, BRB44 and Ly-26 are also being studied. BRB44, produced in our laboratory against an undifferentiated cell line, has a very complex strain distribution pattern among inbred strains of mice and is expressed on mature B and myeloid lineage cells. The BRB44 antibody precipitates a 72kDa, glycosylated protein. Recent characterization of Ly-26.1, has shown that it is variably expressed on most bone marrow cells, mature B lymphocytes and granulocytes/macrophages and on CD8 T cells. Anti-Ly-26 antibodies precipitate 100 or 120 kDa proteins, dependent upon tissue localization.
