Open AccessLoss of BIM in T cells results in BCL-2 family BH3-member compensation but incomplete cell death sensitivity normalization
Author(s) -
Lindsey M. Ludwig,
Lauren E. Roach,
Samuel G. Katz,
James L. LaBelle
Publication year - 2020
Publication title -
apoptosis (london)
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.318
H-Index - 110
eISSN - 1573-675X
pISSN - 1360-8185
DOI - 10.1007/s10495-020-01593-6
Subject(s) - downregulation and upregulation , apoptosis , programmed cell death , biology , tcirg1 , microbiology and biotechnology , bcl xl , puma , cd8 , t cell , thymocyte , t lymphocyte , immunology , immune system , cd28 , genetics , gene
BIM is the master BH3-only BCL-2 family regulator of lymphocyte survival. To understand how long-term loss of BIM affects apoptotic resistance in T cells we studied animals with T cell-specific deletion of Bim. Unlike CD19 CRE Bim fl/fl animals, LCK CRE Bim fl/fl mice have pronounced early lymphocytosis followed by normalization of lymphocyte counts over time. This normalization occurred in mature T cells, as thymocyte development and apoptotic sensitivity remained abnormal in LCK CRE Bim fl/fl mice. T cells from aged mice experienced normalization of their absolute cell numbers and responses against various apoptotic stimuli. mRNA expression levels of BCL-2 family proteins in CD4 + and CD8 + T cells from young and old mice revealed upregulation of several BH3-only proteins, including Puma, Noxa, and Bmf. Despite upregulation of various BH3 proteins, there were no differences in anti-apoptotic BCL-2 protein dependency in these cells. However, T cells had continued resistance to direct BIM BH3-induced mitochondrial depolarization. This study further highlights the importance of BIM in cell death maintenance in T cells and provides new insight into the dynamism underlying BH3-only regulation of T cell homeostasis versus induced cell death and suggests that CD4 + and CD8 + T cells compensate differently in response to loss of Bim.