Regulation of B‐cell entry into the cell cycle

Department of Immunology and Microbiology, University of Washington, Seattle, WA 98195, USA.
Immunological Reviews (Impact Factor: 10.12). 09/2008; 224(1):183-200. DOI: 10.1111/j.1600-065X.2008.00652.x
Source: PubMed

ABSTRACT B cells are induced to enter the cell cycle by stimuli including ligation of the B-cell receptor (BCR) complex and Toll-like receptor (TLR) agonists. This review discusses the contribution of several molecules, which act at distinct steps in B-cell activation. 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, namely Rac1 and the plasma membrane phospholipid PI(3,4)P(2). The co-receptor CD22 can inhibit BCR-induced proliferation by binding to novel CD22 ligands. Finally, regulators of B-cell survival and death also play roles in B-cell transit through the cell cycle. Caspase 6 negatively regulates CD40- and TLR-dependent G(1) entry, while acting later in the cell cycle to promote S-phase entry. Caspase 6 deficiency predisposes B cells to differentiate rather than proliferate after stimulation. Bim, a pro-apoptotic Bcl-2 family member, exerts a positive regulatory effect on cell cycle entry, which is opposed by Bcl-2. New insights into what regulates B-cell transit through the cell cycle may lead to thoughtful design of highly selective drugs that target pathogenic B cells.

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    PLoS ONE 12/2013; 8(12):e84928. DOI:10.1371/journal.pone.0084928 · 3.23 Impact Factor
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    Genome Research 08/2010; 20(8):1064-83. DOI:10.1101/gr.104935.110 · 14.63 Impact Factor
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    • "A completely unexpected finding was the upregulation of RBL2 in early stage B-CLL cells with respect to circulating B lymphocytes (Fig 1A). Although the upregulation of RBL2 expression was counterproductive because the retinoblastoma family members are usually regarded as tumor suppressor genes (Burkhart & Sage, 2008), it is notable that accumulating data have linked RBL2 to a decrease of cell cycle progression and to an upregulation of anti-apoptotic genes (Richards et al, 2008). Consistent with this hypothesis, and in line with previous data (Reed et al, 2002) regarding genes involved in apoptosis, B lymphocytes obtained from B-CLL patients showed a significantly (P < 0AE05) greater expression of the anti-apoptotic Bcl-2 genes, MCL1 and XIAP with respect to normal B cells (Fig 1B). "
    British Journal of Haematology 03/2009; 145(3):424-6; author reply 426-8. DOI:10.1111/j.1365-2141.2009.07589.x · 4.71 Impact Factor
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