Differential Effects of Bcl-2 on T and B Cells in Transgenic Mice

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 89; no. 23; pp. 11376 - 11380
• Main Authors: Katsumata, Makoto, Siegel, Richard M., Louie, Diane C., Miyashita, Toshiyuki, Tsujimoto, Yoshihide, Nowell, Peter C., Greene, Mark I., Reed, John C.
• Format: Journal Article
• Language: English
• Published: Washington, DC National Academy of Sciences of the United States of America 01.12.1992; National Acad Sciences
• Subjects: Animal tumors. Experimental tumors; Animals; B lymphocytes; B-Lymphocytes - cytology; B-Lymphocytes - physiology; Biological and medical sciences; Cell lines; Cell Survival; Experimental malignant blood diseases; Gene Expression; Hematopoiesis; Lymph nodes; Lymph Nodes - cytology; Lymphocytes; Lymphoid tissue; Medical sciences; Mice; Mice, Transgenic; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins c-bcl-2; Spleen; Spleen - cytology; T lymphocytes; T-Lymphocytes - cytology; T-Lymphocytes - physiology; Thymocytes; Transgenes; Transgenic animals; Tumors; Chromosomal aberration; Human; Pathogenesis; Rodentia; Transgenic animal; Malignant hemopathy; B-Lymphocyte; Gene expression; Cell subpopulation; Experimental disease; Vertebrata; Regulation(control); Specificity; Mammalia; Mouse; Cell death; Animal; C-Onc gene; T-Lymphocyte; Follicular lymphoma; Abnormal chromosome; Chromosome translocation
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.89.23.11376

We have produced bcl-2 transgenic mice by using a construct which mimics the t(14;18) translocation in human follicular lymphomas. Although lymphoid tissues from all transgenic mice contained high levels of human Bcl-2 protein, transgene expression was differentially regulated within the B- and T-cell compartments of lines derived from various founder mice. We have characterized the phenotypes of two lines of bcl-2 transgenic mice (line 2 and line 6) in which bcl-2 transgene expression was restricted primarily to the T- or B-cell lineages, respectively. Analysis of line 6 lymphocytes revealed a polyclonal expansion of B cells, and these B cells exhibited prolonged survival in vitro. In line 2 mice, numbers of T cells in the peripheral lymphoid tissues were more moderately elevated despite enhanced T-cell survival in vitro. Line 2 transgenic mice also showed significantly increased proportions of thymocytes with a mature phenotype. Taken together, these findings suggest different roles for bcl-2 in the in vivo regulation of B- and T-cell development and homeostasis.