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Regulation of B cell entry into the cell cycle

B cells are induced to enter the cell cycle by ligation of the B-cell receptor (BCR) complex and by Toll-like receptor (TLR) agonists. B-cell activation is regulated by molecules with several distinct modes of action: A first example, the adapter molecule Bam32 (B-lymphocyte adapter of 32 kDa), helps promote BCR-induced cell cycle entry, while the secondary messenger superoxide has the opposite effect. Bam32 and superoxide may fine tune BCR-induced activation by competing for the same limited resources including Rac1/2 and/or the plasma membrane phospholipid PI(3,4)P2. A second example, the BCR-associated co-receptor CD22, inhibits BCR-induced proliferation by binding to novel CD22 ligands on B cells and dendritic cells. Regulators of B-cell survival and death also influence B-cell transit through the cell cycle. Caspase 6 normally is simply classified as an effector caspase in cell death pathways; but in B cells caspase 6 negatively regulates CD40- and TLR-dependent G1 entry, in part by controlling levels of phosphorylated retinoblastoma (Rb) protein. Caspase 6 deficiency predisposes B cells to differentiate rather than proliferate after stimulation. The Bcl-2 family member, Bim, is normally classified as a 'pro-apoptotic' protein; but in B cells, it exerts a positive regulatory effect on cell cycle entry, which is opposed by Bcl-2. New insights into how B-cell transit through the cell cycle is controlled may lead to thoughtful design of drugs that selectively target pathogenic B cells.

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Correspondence to EA Clark.

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Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution 2.0 International License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Clark, E. Regulation of B cell entry into the cell cycle. Cell Commun Signal 7, A71 (2009).

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  • Cell Cycle
  • Retinoblastoma
  • CD22 Ligand
  • Cell Death Pathway
  • Adapter Molecule