Loss of the proapoptotic protein, Bim, breaks B cell anergy

Loss of the proapoptotic protein, Bim, breaks B cell anergy

Although B cells that respond with high avidity to self-antigen are eliminated early in their development, many autoreactive B cells escape elimination and are tolerized later in their lives via anergy. Anergic B cells are unresponsive to antigen and die prematurely. It has been suggested that the proapoptotic protein, Bim, controls the fate of anergic B cells. To test this idea, mice lacking B...

Proapoptotic BIM Impacts B Lymphoid Homeostasis by Limiting the Survival of Mature B Cells in a Cell-Autonomous Manner

The proapoptotic BH3-only protein BIM (Bcl2l11) plays key roles in the maintenance of multiple hematopoietic cell types. In mice, germline knockout or conditional pan-hematopoietic deletion of Bim results in marked splenomegaly and significantly increased numbers of B cells. However, it has remained unclear whether these abnormalities reflect the loss of cell-intrinsic functions of BIM within t...

Proapoptotic protein Bim attenuates estrogen-enhanced survival in lymphangioleiomyomatosis.

Lymphangioleiomyomatosis (LAM) is a progressive lung disease that primarily affects young women. Genetic evidence suggests that LAM cells bearing TSC2 mutations migrate to the lungs, proliferate, and cause cystic remodeling. The female predominance indicates that estrogen plays a critical role in LAM pathogenesis, and we have proposed that estrogen promotes LAM cell metastasis by inhibition of ...

The Proapoptotic Bcl-2 Family Member Bim

Loss of Bim Allows Precursor B Cell Survival But Not Precursor B Cell Differentiation in the Absence of Interleukin 7

Interleukin (IL)-7 is a stromal cell-derived cytokine required for the survival, proliferation, and differentiation of B cell precursors. Members of the Bcl-2 family of proteins are known to have profound effects on lymphocyte survival, but not lymphocyte differentiation. To distinguish the relative dependence on IL-7 of B cell precursor survival versus B cell differentiation, the combined effe...