IMMUNOGLOBULIN STRUCTURE & DIVERSITY--CHARACTERIZATION OF CELL MEMBRANE PROTEINS

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(1) A SCID mouse colony has been established to examine in vivo aspects of both neoplastic and normal development. In the first instance, this system is being used to analyze the basic genetic requirements for plasmacytoma induction. SCID mice have been reconstituted with bone marrow from either susceptible or resistant strains and have been subjected to tumor induction protocols to determine the relative contributions of genetic background versus potential B-cell defects in the induction process. The SCID model is also being used to assess the genetic potential of various normal lymphocyte populations through appropriate reconstitution experiments. (2) The initial development of plasmacytomas has been difficult to study due to the inability to grow early stage tumors in culture or prevent them from progressing to later stage phenotypes. This problem has now been significantly lessened by the demonstrated ability to grow primary plasmacytomas in vitro on feeder layers consisting of autologous adherent cells derived from the same tumor. Characterization of these feeders and their interactions with plasmacytoma cells are currently being evaluated. (3) Two longstanding studies of genes that regulate the differentiation of hematopoietic cells have continued. In the first system it was shown that a number of events including production of GM-CSF and IL-6, down regulation of myb and up regulation of fos and fms mRNA transcripts and changes in CD45 isoform expression may contribute to the switch to myeloid differentiation by bipotential B lymphocyte progenitors. A detailed study of CD45 isoform expression during development of B lymphocytes and myeloid cells was initiated. Further studies of mice homozygous for lpr or gld, two genes that interfere with normal T cell differentiation and function, showed that following cross linking of the TcR, the expanded DN T cells were unable to produce a spectrum of lymphokines, whereas the diluted CD4+ T cells overproduced lymphokines involved in inflammatory responses and thus may contribute to the development of autoimmune disease.