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Eur Cytokine Netw. 2002 Oct-Dec;13(4):439-45.

Differential modulation of interleukin-2-and interleukin-4-mediated early activation of normal human B lymphocytes by the caspase inhibitor zVAD-fmk.

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1
INSERM U.542, Hôpital Paul Brousse, Bâtiment Lavoisier, 14 Avenue Paul Vaillant Couturier, 94807 Villejuif Cedex, France.

Abstract

Caspases are a group of cysteine-related proteases that control the process of apoptosis and may also be involved in the control of lymphocyte activation. We show here that the broad-spectrum caspase inhibitor benzyloxycarbonyl (Cbz)-Val-Ala-Asp (Ome)-fluoromethylketone (zVAD-fmk) prevents the proliferation of resting human B tonsilar lymphocytes mediated by the B cell mitogen SAC or the combination of anti-mu Ab and IL-2. zVAD-fmk inhibits IL-2-induced phosphorylation of the retinoblastoma protein, and cyclin D2 expression. However, neither the IL-2-mediated proliferation of cycling activated B cells nor that of lymphoma cells were inhibited by zVAD-fmk, suggesting that only the early steps of SAC- or IL-2-mediated B cell activation were sensitive to the inhibitory properties of zVAD-fmk. Our data also demonstrated that the inhibitory effect of zVAD-fmk was not observed when B cells were activated with IL-4 in the presence of either anti-mu Ab or anti-CD40 Ab. Thus, our results suggest that caspase activation is required for the IL-2-mediated entry of primary B lymphocytes into the cell cycle and show that caspase activation plays different roles in IL-2- and IL-4-mediated B cell proliferation.

PMID:
12517729
[Indexed for MEDLINE]
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