We will study the genetics of susceptibility to antigen-driven lymphomagenesis in B10.H-2?a?H-4?b? p/Wts (2?a?4?b?) mice. The objective is to determine whether a gene(s) associated with H-2?a? and/or H-4?b? determines susceptibility and/or whether an unlinked mutant gene is involved. The methods to be used are those of conventional Mendelian genetics employing segregation and linkage analysis. We will attempt to drive lymphomagenesis in 2?a?4?b? mice with antigens other than sheep erythrocytes (SRBC) to determine whether B-cell lymphomas bearing surface immunoglobulin specific for such antigens can be obtained and to delineate the range of preneoplastic B-cell clones occurring in 2?a?4?b? mice. The methods will employ hyperimmunization followed by syngeneic spleen cell transfer, as has proven successful with SRBC. We will continue to analyze the differentiation phenotype, the immunoglobulin gene arrangements, and the immunoglobulin idiotypes of the CH series of B-cell lymphomas in an attempt to understand the mechanism of antigen-driven lymphomagenesis and the possibility of a specific regulatory defect in 2?a?4?b? mice. The methods to be employed include PAGE of DNA restriction enzyme digests, computer analysis of flow cytometry data, and amino acid sequence analysis. We will utilize our growing collection of CH series B-cell lymphomas bearing surface immunoglobulin of known antigen reactivity to study the influence of mitogens, T-cell subsets and factors, and specific ligands on induced differentiation of B cells. The principle method to be used in these studies is that of Cunningham for enumeration of plaque-forming cells. (AG)
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