This proposal focuses on the differentiation and activation of the mouse B lymphocyte lineage. Extensive use will be made of B cell progenitor-reconstituted investigate the in vivo regulation of B cell differentiation by T cells and other cell types. The sites of localization and the functional capacity of B cells generated in this adoptive transfer model will be determined. The role of the Lyb-2 surface molecule in the regulation of early B cell differentiation will be evaluated. A large fraction of newly- formed B cells fail to survive for more than 24-48 hours, and we will evaluate hypotheses regarding the mechanism of this cell death. We will examine the effect of antigen or anti-idiotypic stimulation on the survival of newly emerging specific B cells and on the relative expression of different antibody specificities. We also will continue to study the details of T cell:B cell collaboration during the course of in vitro antibody responses. Our previous evidence suggests that prolonged T:B contact is required for the induction of antibody synthesis by small B cells, and we will perform experiments that involve disruption of T:B conjugates formed between cloned helper T cells and immunoglobulin transgenic B cells to determine the duration and importance of these interactions. These experiments will use mice as the experimental animal, and should yield important new information on the control of B cell differentiation, the relationship of various B cell subsets, and the mechanism of T:B cell collaboration.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
7R01AI022871-08
Application #
3134497
Study Section
Immunobiology Study Section (IMB)
Project Start
1985-04-01
Project End
1994-03-31
Budget Start
1992-07-01
Budget End
1994-03-31
Support Year
8
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Scripps Research Institute
Department
Type
DUNS #
City
La Jolla
State
CA
Country
United States
Zip Code
92037
Rochford, R; Mosier, D E (1995) Differential Epstein-Barr virus gene expression in B-cell subsets recovered from lymphomas in SCID mice after transplantation of human peripheral blood lymphocytes. J Virol 69:150-5
Van Kuyk, R; Mosier, D E (1995) Lack of pseudotype formation between human immunodeficiency virus type 1 and Epstein-Barr virus in productively coinfected B lymphoblastoid cell lines. Virology 209:643-8
Riggs, J E; Feeney, A J; Kirven, M et al. (1994) VH11 bias and normal V-D-J junctions in SCID B lymphocytes rescued by neonatal T cell transfer. Mol Immunol 31:783-91
Picchio, G R; Cohen, J I; Wyatt, E R et al. (1993) Enhanced tumorigenicity of an Epstein-Barr virus-transformed lymphoblastoid cell line is associated with a unique 1:18 chromosomal translocation and decreased expression of lymphocyte function associated antigen-1a (CD11A). Am J Pathol 143:342-9
Mosier, D E; Stell, K L; Gulizia, R J et al. (1993) Homozygous scid/scid;beige/beige mice have low levels of spontaneous or neonatal T cell-induced B cell generation. J Exp Med 177:191-4
Feeney, A J (1992) Comparison of junctional diversity in the neonatal and adult immunoglobulin repertoires. Int Rev Immunol 8:113-22
Cohen, J I; Picchio, G R; Mosier, D E (1992) Epstein-Barr virus nuclear protein 2 is a critical determinant for tumor growth in SCID mice and for transformation in vitro. J Virol 66:7555-9
Picchio, G R; Kobayashi, R; Kirven, M et al. (1992) Heterogeneity among Epstein-Barr virus-seropositive donors in the generation of immunoblastic B-cell lymphomas in SCID mice receiving human peripheral blood leukocyte grafts. Cancer Res 52:2468-77
Riggs, J E; Hobbs, M V; Mosier, D E (1992) CD4+CD8- thymocytes from neonatal mice induce IgM production in SCID mice. J Immunol 148:1389-95
Thangavelu, M; Snyder, L; Anastasi, J et al. (1992) Cytogenetic characterization of B-cell lymphomas from severe combined immunodeficiency disease mice given injections of lymphocytes from Epstein-Barr virus-positive donors. Cancer Res 52:4678-81

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