Showing papers by "Mark M. Davis published in 1982"

Molecular cloning of translocations involving chromosome 15 and the immunoglobulin C alpha gene from chromosome 12 in two murine plasmacytomas

Abstract: Expression of IgA by plasmacytomas occurs as a result of a DNA rearrangement that brings the variable region gene, VH, a few kilobases 5' to the constant region gene, C alpha. In this study, we show that the allelic nonexpressed C alpha gene also is rearranged in most plasmacytomas. Cloning, restriction mapping, heteroduplex analyses, and sequence analyses of the nonproductively rearrange C alpha genes from two plasmacytomas, M603 and M167, have demonstrated that the nonproductive rearrangement occurs within the alpha switching region, S alpha. In each case, the same DNA sequence has been joined to the 5' side of C alpha and we have termed this DNA "NIRD" (for nonimmunoglobulin rearranged DNA). Southern blotting analyses of genomic DNAs from various IgG-, IgM-, or IgA-producing plasmacytomas suggest that NIRD is rearranged in almost all plasmacytomas. However, NIRD rearranges to the S alpha region only in IgA-producing cells, not in IgM or IgG producers. Cytogenetic evidence has shown that T(12;15) translocations are common in murine plasmacytomas. Immunoglobulin heavy chain genes are located on chromosome 12, and the translocation breakpoint in plasmacytomas occurs near the immunoglobulin genes. NIRD has been mapped to chromosome 15 by Southern blotting analysis of mouse-hamster cell lines, suggesting that the nonproductively rearranged C alpha clones represent the T(12;15) translocations identified cytogenetically. Therefore, we have identified a region of DNA on chromosome 15 that is commonly rearranged in transformed mouse lymphocytes. We speculate on the significance of NIRD in neoplastic transformation of mouse lymphocytes.

Wehi-231 as a tumor model for tolerance induction in immature b lymphocytes

Abstract: WEHI-231 is a murine B lymphoma cell line with a surface marker phenotype similar to that of immature B lymphocytes. Its growth is inhibited by exposure to anti-IgM antibodies. This process is complete and irreversible and is not exhibited by B lymphoma cell lines which express more “mature” phenotypes. Lipopolysaccharide protects WEHI-231 against anti-IgM-induced growth inhibition. This state of protection, although transient may represent a differentiation of WEHI-231 cells to a more mature state. This growth inhibition by anti-μ and protection against it by LPS may provide a tumor model to examine tolerance induction and differentiation of immature B cells.

The isolation of b and t cell-specific genes

Abstract: Our understanding of lymphocyte differentiation and function would be greatly increased if we could isolate and characterize the specific genes involved. Towards this end we have measured the differences in gene expression between B and T cell lymphomas and developed procedures for systematically isolating the genes which make up these differences. Specifically we have found that B and T cell tumors differ by about 2% of the mass of their mRNA and that this corresponds to approximately 200 different genes present in one type of cell but not the other. We have also shown that the cDNA probes corresponding to this 2% difference (either B cell specific, B * -T, or T cell specific, T * -B): 1) are representative of genes expressed in normal tissues (spleen and thymus); 2) can be used to screen recombinant libraries and isolate B or T cell specific cDNA clones; and 3) can be cloned directly into plasmids, resulting in whole libraries of B or T cell specific genes. Additionally, we find a striking correlation between lineage relationships and gene expression; that is, cells which are closely related in terms of lineage are also closely related in terms of gene expression.