Caspase activity is required for stimulated B Lymphocytes to enter the cell cycle

N. Eric Olson, Jonathan D. Graves, Geraldine L. Shu, Elizabeth J. Ryan, Edward A. Clark

Research output: Contribution to journalArticlepeer-review

Abstract

Following activation with proliferative stimuli, including ligation of CD40, dense human tonsillar B cells (>98% cells in G0) have increased cleavage and activation of caspase-8 and -6 accompanied by decreased caspase-3 activation and apoptosis. Proliferation was blocked by either a broad specificity caspase inhibitor or inhibitors selective for caspase-6 or caspase-8. In contrast, an inhibitor selective for caspase-3 was without effect. Furthermore, induction of cyclin D and cyclin-dependent kinase 4 mRNA and protein was blocked upon inhibition of caspase-6, but not caspase-3. Thus, caspase-6-like activity is required for quiescent B cells to increase the expression of genes required for entry into G1. In support of this model, the transcriptional suppressor special AT-rich sequence-binding protein 1, a preferred caspase-6 substrate, was cleaved upon B cell stimulation. Caspase activity was not required for all signaling events, as caspase inhibitors did not affect the phosphorylation of p42/44 mitogen-activated protein kinase, the expression of the survival factor cellular inhibitor of apoptosis 2, or the production of IL-6 by stimulated G0. B cells. These findings suggest a mechanism by which caspase-6 may selectively allow entry of quiescent B cells into the cell cycle.

Original languageEnglish
Pages (from-to)6065-6072
Number of pages8
JournalJournal of Immunology
Volume170
Issue number12
DOIs
Publication statusPublished - 15 Jun 2003
Externally publishedYes

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