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The roles of Bim and Bmf in B-cell development and apoptosis in TACI-lg transgenic mice

 

The development of B cells relays on two interconnected survival pathways, B-cell receptor (BCR) and the BAFF receptor (BAFF-R), and both are essential for normal B-cell development. Mechanically, BCR-dependent survival are mainly regulated by AKT/PI3K pathway, while BAFF/BAFF-R-mediated survival involves non-canonical NF-κB, MAPK/ERK as well as AKT/PI3K signaling pathways. Plasma cell survival is regulated by APRIL following NF-κB activation via transmembrane activator together with CAML interactor (TACI) or B-cell maturation (BCMA). On the other hand, how do these signaling molecules trigger B-cell apoptosis remains largely unknown. Woess et al. demonstrated B-cell lymphoma 2 (Bcl2) interacting mediator of cell death (Bim) and Bcl2 modifying factor (Bmf), the two pro-apoptotic members of Bcl2 family, mediate apoptosis in the context of lacking BAFF and APRIL. The article was published in Cell Death and Differentiation.

 

The effectively neutralization of BAFF and APRIL results from TACI-lg overexpression. They found Bcl2 transgenic B cells susceptible to the effects of TACI-lg expression, resulting in attenuates pathology in Vav-Bcl2 transgenic mice. The findings suggest Bim and Bmf, two Bacl2 antagonists, can enhance the effect of BAFF/APRIL-depletion therapeutic strategies in B-cell malignancies.

 

Reference:
Cell Death Differ. 2015 Feb 20. doi: 10.1038/cdd.2015.8.

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