The repertoire of glycoproteins expressed on the plasma membrane of lymphoid cells reflects their state of differentiation and maturation. Many of these molecules were first identified using monoclonal antibodies raised against neoplastic cells. In the case of non T, non B acute lymphoblastic leukemia cells, several membrane antigens have been identified whose expression on lymphocytes is limited to the early B lineage. The physiologic function of these gene products is unknown. Four of these antigens are represented in single polypeptides and thus appear to be encoded by single genes. The low level of expression of these gene products suggests that they are encoded by RNA transcripts which are present in low abundance. We, therefore, propose to use DNA-mediated gene transfer to express the genes encoding human B lymphocyte differentiation antigens in mouse cell lines. The donor human DNA sequences will be isolated by serial DNA transfection and will be molecularly cloned. Restriction fragments lacking highly repetitive human DNA sequences will be identified and are expected to contain the coding sequences (exons) expressed in spliced, polyadenylated messenger RNAs. The detection of such sequences in cDNA libraries provides an alternative approach to cloning rare transcripts and determining their nucleotide sequence. The first detailed characterization of genes encoding proteins whose expression in clonal hematopoietic malignancies is of diagnostic significance will provide the necessary tools to evaluate the expression of these genes in normal B cell development.
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