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Eur J Immunol. 2005 Mar;35(3):971-6.

Endogenous association of Bim BH3-only protein with Mcl-1, Bcl-xL and Bcl-2 on mitochondria in human B cells.

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INSERM, UMR601, Département de Recherche en Cancérologie, Equipe 5 labélisée L N C, Institut de Biologie, Nantes, France.


Bim is an essential regulator of lymphoid system homeostasis and appears essential for B cell apoptosis induction. The mechanism by which Bim isoforms are held in an inactive form remains poorly documented in normal B cells. In the current study, we demonstrated that in normal tonsil B cells the three major Bim isoforms are strongly associated with the anti-apoptotic Bcl-2 family members Mcl-1, Bcl-2 and Bcl-x(L). On the other hand, only a weak association of BimEL and L with the dynein LC8 chain has been found. In addition, there is no free Bim in normal B cells. Moreover, subcellular fractionation demonstrated that Bim and the anti-apoptotic counterparts are localized preferentially in the mitochondria-rich fraction. The fact that most Bim was found in this fraction supports the hypothesis that it is sequestered by anti-apoptotic molecules in mitochondria where its pro-apoptotic activity is controlled. Of interest, BimS is essentially complexed to Mcl-1 and the Mcl-1/Bim complex is the most abundant among the three types of complexes. This supports the idea that this complex is critical for the control of B cell death. In conclusion, these results favor a model in which Bim release from anti-apoptotic proteins is a critical event for initiation of apoptosis.

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