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. LIP-6 is expressed by bone marrow cells, B lineage cells and macrophages but absent on all T lineage cells. Experiments have shown that 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. In addition, a population of bone marrow cells has been identified by its expression of LIP-6. Characterization of this LIP-6 precursor population by combined genetic and biological assays suggest this population is an immature progenitor population with limited differentiation capacity within the B cell lineage and perhaps the myeloid lineage. Future studies will further characterize the LIP-6 antigen and 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-26.1 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. Activation of B cells, as occurs in mice with MAIDS, induces the expression of BRB44 on B cells and CD4+ cells in B6, BRB44lo mice, suggesting that BRB44 is an activation antigen. Recent characterization of a previously described antigen, Ly- 26.1, has shown that it is variably expressed on most bone marrow cells, mature B lymphocytes and granulocytes/macrophages and on CD4+ T cells. Interestingly, the binding of antibodies to the Mac-1(CD11b) surface antigen is blocked by anti-Ly26.1 antibodies. These data and preliminary biochemical data suggest that Ly-26.1 may be co-associate with Mac-1 on the surface of myeloid lineage cells.
