The aim of the proposed studies is to analyze the role of the murine Fc receptor complex in B cell differentiation and triggering. Specifically, we will attempt to clone and sequence the gene coding for Lym20.2, a serologically detectable B cell marker that represents an allelic form of the Fc receptor molecule. This gene is either identical or very closely linked to the gene coding for the Mls molecule that has important T cell triggering functions. The precise analysis of the genomic organization and function of this cluster of B cell differentiation antigens will give insights into the molecular mechanism of T cell-B cell interaction. Furthermore, it will provide gene probes that allow the characterization of human B cell malignancies, which represents the long term significance of this project. We will construct genomic transfection libraries in heterologous species of fibroblasts, using chromosomal DNA from Lym20.2+ tissue, and select for stable transfectants that express Lym20. We will then prepare specific subtractive cDNA probes, in order to screen cDNA and genomic cosmid libraries for the Lym20 gene. In parallel, we will use synthetic oligonucleotide probes whose sequence is deduced from a partial amino acid sequence of the Lym20.2 molecule. Having established the identity of the selected cDNA and cosmid clones in chromosomal mapping and transfection experiments, we will analyze the relationship between the Lym20/Fc receptor molecule and the Mls gene product. Finally, we will analyze the mechanism by which Mls alleles control induction of T cell proliferation.
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