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

Eur J Immunol. 2005 Mar;35(3):971-6. doi: 10.1002/eji.200425878.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / physiology
  • Apoptosis Regulatory Proteins
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism*
  • Bcl-2-Like Protein 11
  • Carrier Proteins / immunology
  • Carrier Proteins / metabolism*
  • Cells, Cultured
  • Humans
  • Immunoblotting
  • Immunoprecipitation
  • Membrane Proteins / immunology
  • Membrane Proteins / metabolism*
  • Mitochondria / immunology
  • Mitochondria / metabolism*
  • Myeloid Cell Leukemia Sequence 1 Protein
  • Neoplasm Proteins / immunology
  • Neoplasm Proteins / metabolism*
  • Palatine Tonsil / cytology
  • Protein Isoforms / immunology
  • Protein Isoforms / metabolism
  • Proto-Oncogene Proteins / immunology
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins c-bcl-2 / immunology
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • bcl-X Protein


  • Apoptosis Regulatory Proteins
  • BCL2L1 protein, human
  • BCL2L11 protein, human
  • Bcl-2-Like Protein 11
  • Carrier Proteins
  • Membrane Proteins
  • Myeloid Cell Leukemia Sequence 1 Protein
  • Neoplasm Proteins
  • Protein Isoforms
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-X Protein