The overall goal of this proposal is to analyze expression of immunoglobulin (Ig) in spontaneous, chemically-induced, and virus-induced B-lymphoma tumors and cloned tissue culture cell lines which serve as models for various stages in the normal B-lymphocyte differentiation scheme. We will construct somatic cell hybrids between "wild type" and variant B-lymphoid cell lines representing the same or different stages of B-lymphocyte development. We will also construct somatic cell hybrids between B-lymphoid cell lines and normal lymphoid cells. Construction of these somatic cell hybrids will serve to generate new cell lines and will also facilitate analysis of the regulation of Ig gene expression and B-cell differentiation. Specific experiments are proposed to elucidate several unusual features of Ig gene expression: 1) induction of mu heavy (H) chain expression in an Ig negative lymphoid cell line, 2) induction of light (L) chain expression in a pre-B cell line which already expresses a "cytoplasmic" mu H chain, 3) allelic exclusion of L chain, 4) simultaneous expression of discrete secreted and surface gamma 2a H chain species by a cloned B-lymphoid cell, and 5) simultaneous expression of mu and gamma 2a H chains by a cloned B-lymphoid cell line. We will attempt to construct somatic cell hybrids which express surface Ig directed against a specific antigen, and try to induce these hybrids to differentiate in an appropriate in vivo or in vitro microenvironment.
NIH ExPorter
NIH ExPorter