Loss of Bim allows precursor B cell survival but not precursor B cell differentiation in the absence of interleukin 7

J Exp Med. 2004 Nov 1;200(9):1179-87. doi: 10.1084/jem.20041129.

Abstract

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 effects of lack of IL-7 and lack of the proapoptotic Bcl-2 relative, Bim, were studied. Bim is expressed to varying degrees in all B cell precursors and B cells. Lack of Bim compensated for lack of IL-7 in the survival of pro-, pre-, and immature B cells; however, lack of Bim did not substitute for the requirement for IL-7 in B cell precursor differentiation or B cell precursor proliferation. Precursor B cell survival is more dependent on sufficient levels of IL-7 than precursor B cell differentiation because the number of B cells and their precursors were reduced by half in mice heterozygous for IL-7 expression, but were restored to normal numbers in mice also lacking Bim. Hence, Bim and IL-7 work together to control the survival of B cell precursors and the number of B cells that exist in animals.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Apoptosis Regulatory Proteins
  • B-Lymphocytes / cytology*
  • B-Lymphocytes / immunology
  • Bcl-2-Like Protein 11
  • Bone Marrow Cells / immunology
  • Carrier Proteins / immunology*
  • Carrier Proteins / metabolism
  • Cell Differentiation / immunology*
  • Cell Survival / immunology
  • DNA, Complementary / genetics
  • Flow Cytometry
  • Fluoresceins
  • Interleukin-7 / genetics
  • Interleukin-7 / immunology*
  • Membrane Proteins / immunology*
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Mutant Strains
  • Proto-Oncogene Proteins / immunology*
  • Proto-Oncogene Proteins / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Succinimides

Substances

  • 5-(6)-carboxyfluorescein diacetate succinimidyl ester
  • Apoptosis Regulatory Proteins
  • Bcl-2-Like Protein 11
  • Bcl2l11 protein, mouse
  • Carrier Proteins
  • DNA, Complementary
  • Fluoresceins
  • Interleukin-7
  • Membrane Proteins
  • Proto-Oncogene Proteins
  • Succinimides