Promotion of activated human B cell apoptosis and inhibition of Ig production by soluble CD95 ligand: CD95-based downregulation of Ig production need not culminate in activated B cell death

William Stohl, Dong Xu, Gary C. Starling, Paolo Casali, Peter A. Kiener

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

CD95/CD95L interactions are vital to normal lymphoid homeostasis and in the protection against autoimmunity. To directly assess the effects of CD95L on activated B cell survival and Ig responses, purified human peripheral blood B cells, activated in vitro with SAC + rIL2, were incubated with a soluble CD95L fusion protein (fp) and assayed for apoptosis and IgG/IgM production. CD95L fp reproducibly increased apoptosis of these activated B cells and inhibited their Ig production. However, CD95L fp-mediated effects on activated B cell survival could be uncoupled from those on Ig production in that a soluble CD40L fp was incapable of reversing CD95L fp-mediated downregulation of Ig responses despite inhibiting CD95L fp-mediated apoptosis. Moreover, despite the specific caspase-8 inhibitor z-IETD-fmk substantially protecting transformed CL-01 B cells from CD95L fp-mediated apoptosis and permitting their ongoing proliferation, caspase-8 inhibition had no protective effects on CD95L fp-mediated inhibition of constitutive IgM production by CL-01 B cells. Collectively, these results point to a CD95-based downregulatory pathway in activated B cells that need not necessarily culminate in their death. (C) 2000 Academic Press.

Original languageEnglish (US)
Pages (from-to)1-11
Number of pages11
JournalCellular Immunology
Volume203
Issue number1
DOIs
StatePublished - Jul 10 2000
Externally publishedYes

Keywords

  • Apoptosis
  • B cells
  • CD95
  • CD95 ligand
  • Ig production

ASJC Scopus subject areas

  • Immunology

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