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)

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA023770-07
Application #
3166234
Study Section
Immunobiology Study Section (IMB)
Project Start
1979-01-01
Project End
1987-03-31
Budget Start
1985-04-01
Budget End
1986-03-31
Support Year
7
Fiscal Year
1985
Total Cost
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Type
Schools of Medicine
DUNS #
078861598
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
Whitmore, A C; Prowse, D M; Haughton, G et al. (1991) Ig isotype switching in B lymphocytes. The effect of T cell-derived interleukins, cytokines, cholera toxin, and antigen on isotype switch frequency of a cloned B cell lymphoma. Int Immunol 3:95-103
Pennell, C A; Maynard, E; Arnold, L W et al. (1990) High frequency expression of S107 VH genes by peritoneal B cells of B10.H-2aH-4bP/WTS mice. J Immunol 145:1592-7
Bishop, G A; Pennell, C A; Travis, W et al. (1990) Antibodies specific for Ig idiotype, but not isotype, can substitute for antigen to induce IgM secretion by a B cell clone. Int Immunol 2:285-90
Van Houten, N; Haughton, G (1990) Simultaneously arising Ly-1(CD5) B cell lymphomas have identical expressed IgH and kappa-genes but different nonproductive heavy chain rearrangements. J Immunol 144:745-51
Whitmore, A C; Prowse, D M; Arnold, L W et al. (1989) Ig isotype switching in B lymphocytes. A method for estimating isotype switch frequency in cloned B cell lymphomas. Int Immunol 1:532-9
Van Houten, N; Willoughby, P B; Arnold, L W et al. (1989) Early commitment to neoplasia in murine B- and T-cell lymphomas arising late in life. J Natl Cancer Inst 81:47-54
Pennell, C A; Sheehan, K M; Brodeur, P H et al. (1989) Organization and expression of VH gene families preferentially expressed by Ly-1+ (CD5) B cells. Eur J Immunol 19:2115-21
Mercolino, T J; Locke, A L; Afshari, A et al. (1989) Restricted immunoglobulin variable region gene usage by normal Ly-1 (CD5+) B cells that recognize phosphatidyl choline. J Exp Med 169:1869-77
Pennell, C A; Mercolino, T J; Grdina, T A et al. (1989) Biased immunoglobulin variable region gene expression by Ly-1 B cells due to clonal selection. Eur J Immunol 19:1289-95
Arnold, L W; Grdina, T A; Whitmore, A C et al. (1988) Ig isotype switching in B lymphocytes. Isolation and characterization of clonal variants of the murine Ly-1+ B cell lymphoma, CH12, expressing isotypes other than IgM. J Immunol 140:4355-63

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