A role for intracellular ph in membrane igm-mediated cell death of human B lymphomas

R. Marches, E. S. Vitetta, J. W. Uhr

Research output: Contribution to journalArticle

37 Scopus citations

Abstract

We show that anti-lgM-induced cell death in a human B lymphoma cell line, B104, is associated with early intracellular acidification and cell shrinkage. In contrast, another human B cell lymphoma line, Daudi, less susceptible to B cell antigen receptor-mediated cell death, responded to anti-lgM with an early increase in intracellular pH (pHi). The anti-lgM-induced changes of phi were associated with different levels of activation of the Na+/H+ exchanger isoform 1 (NHE1) as judged by its phosphorylation status. Prevention of anti-lgM-induced cell death in B104 cells by the calcineurin phosphatase inhibitor, cyclosporin A, abrogated both intracellular acidification and cell shrinkage and was associated with an increase in the phosphorylation level of NHE1 within the first 60 min of stimulation. This indicates a key role for calcineurin in regulating phi and cell viability. The potential role of phi in cell viability was confirmed in Daudi cells treated with an Na+/H+ exchanger inhibitor 5-(N,N-hexamethylene)amiloride. These observations indicate that the outcome of the anti-lgM treatment depends on NHE1controlled pHi. We suggest that inactivation of the NHE1 in anti IgM-stimulated cells results in intracellular acidification and subsequently triggers or amplifies cell death.

Original languageEnglish (US)
Pages (from-to)3434-3439
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume98
Issue number6
DOIs
StatePublished - Mar 13 2001

Keywords

  • B cell receptor
  • Na/H exchanger

ASJC Scopus subject areas

  • General

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