| The murine BP-1 antigen is a cell surface glycoprotein formed by two disulfide-linked monomers of 140 kDa. It is expressed on normal and transformed early B-lineage cells, and its level of expression is increased on transformed counterparts of these cells (Cooper, M. D. et al., 1986). The BP-1 molecule is further characterized in the studies included in this dissertation. BP-1 was shown to be a phosphorylated glycoprotein, suggesting that it may play a role in signal transduction. It is biochemically indistinguishable from the transformation-associated early B cell antigen, 6C3. A comparative study suggested that the BP-1 and 6C3 antibodies react with distinct epitopes on the same protein. In vivo tumorigenicity analysis of a group of BP-1/6C3{dollar}sp+{dollar} and BP-1/6C3{dollar}sp-{dollar} Abelson murine leukemia virus (A-MuLV) transformants demonstrated that the expression of this antigen is not necessarily required for malignant transformation. A parallel analysis of BP-1/6C3 expression and the immunoglobulin gene configuration was undertaken, using a panel of A-MuLV transformants, in order to identify any association between these two events. Although no strict correlation was found, these studies showed that many pre-B cells which have undergone VDJ rearrangement acquired this marker. Therefore, at least for A-MuLV transformants, BP-1/6C3 is a good indicator of this differentiative event. Finally, cDNAs encoding BP-1/6C3 antigen were isolated and characterized. A major 4.1 kb BP-1/6C3 mRNA was detected in murine BP-1/6C3{dollar}sp+{dollar} cell lines and in a human pre-B cell line. The cDNA sequence predicts a 945 amino acid type II integral membrane protein that is composed of a 17 amino acid N-terminal cytoplasmic domain, a 22 amino acid membrane-spanning domain and a 906 amino acid C-terminal extracellular domain where a typical zinc-binding motif was identified. The BP-1/6C3 antigen found on early B-lineage cells shares significant homology (36%) to human aminopeptidase N and therefore may be a novel member of the zinc-dependent metallopeptidase gene family. |
