The apoptosis and proliferation of SAC-activated B cells by IL-10 are associated with changes in Bcl-2, Bcl-xL, and Mcl-1 expression

Cell Immunol. 1997 May 25;178(1):33-41. doi: 10.1006/cimm.1997.1129.


Interleukin-10 (IL-10), a cytokine from mouse Th2 cells and macrophage that inhibits IL-2 and IFN-gamma production by Th1 cells, has been reported to stimulate growth and differentiation of B cells activated by CD40 or antigen receptor crosslinking. Our early observation revealed that IL-10 had B cell growth factor (BCGF) activity in human B cells preactivated with SAC or anti-Ig. The responsiveness of the preactivated B cells to IL-10 greatly increased when B cells were activated in the presence of IL-2, whereas IL-10 has no BCGF activity when added at the initiation of activation by SAC. To investigate the dual effects (proliferation and apoptosis) of IL-10 on B cells, the expression of a panel of bcl-2 protoncogene family members, bcl-2, bcl-x, mcl-1, and bax, was analyzed when B cells were activated by SAC. Bcl-xL protein was not expressed in the small resting B cells but was induced by SAC stimulation, reaching its peak at 48 hr. The addition of IL-2 further augmented the Bcl-xL expression with the same kinetics, whereas Bcl-2 and Mcl-1 were expressed by resting B cells and enhanced by SAC stimulation. However, the addition of IL-10 at the initiation of activation down-regulated Bcl-xL, Bcl-2, and Mcl-1 expression. At the same time, B cell proliferation was inhibited and apoptotic cell number increased, suggesting the growth arrest and/or apoptosis of B cells. The apoptosis of SAC-activated B cells by IL-10 was further confirmed by propidium iodide-staining and Annexin V-FITC-staining methods. In contrast, IL-10 failed to down-regulate the Bcl-xL and Bcl-2 expression but rather augmented the expression of Mcl-1 of B cells after preactivation for 48 hr with SAC and IL-2. Under this culture condition, B cells responded to IL-10 to proliferate and differentiate, while IL-2 and IL-10 had an additive or synergistic effect. Taken together, our data suggest that IL-10 acts on the induction stage of Bcl-xL expression and regulates the apoptosis and proliferation of SAC-activated B cells through their bcl-2 family gene expression.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • B-Lymphocytes / immunology*
  • Cell Differentiation / drug effects
  • Cell Division / drug effects
  • Gene Expression Regulation / drug effects*
  • Humans
  • Interleukin-10 / pharmacology*
  • Lymphocyte Activation*
  • Mice
  • Myeloid Cell Leukemia Sequence 1 Protein
  • Neoplasm Proteins / biosynthesis*
  • Neoplasm Proteins / genetics
  • Proto-Oncogene Proteins / biosynthesis*
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins c-bcl-2 / biosynthesis*
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Recombinant Proteins / pharmacology
  • Staphylococcus aureus / immunology*
  • bcl-2-Associated X Protein
  • bcl-X Protein


  • BAX protein, human
  • BCL2L1 protein, human
  • Bax protein, mouse
  • Bcl2l1 protein, mouse
  • Mcl1 protein, mouse
  • Myeloid Cell Leukemia Sequence 1 Protein
  • Neoplasm Proteins
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Recombinant Proteins
  • bcl-2-Associated X Protein
  • bcl-X Protein
  • Interleukin-10