Molecular signals in B cell activation. I. Differential refractory effects of incomplete signaling by lonomycin or PMA relate to autocrine IL-2 production and IL-2R expression

Anand Lagoo, Chien-Te Tseng, Stewart Sell

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Abstract

The molecular signals required by resting (G0) B cells for the induction of cell cycle entry, IL-2 production, and high-affinity IL-2 receptor (IL-2R) expression were defined and the effects of incomplete activation signals on the subsequent response to complete signals were examined. Highly enriched rabbit peripheral blood B cells were activated with a calcium ionophore, ionomycin, and a protein kinase C (PKC) activating phorbol ester, phorbol myristate acetate (PMA). It was observed that cell cycle entry to early G1 was induced by either reagent acting alone, but both reagents were required to stimulate IL-2 production, IL-2R expression, and DNA synthesis. These effects of ionomycin and PMA were shown to be mediated by increased intracellular calcium ion concentration [Ca2+]i and PKC activation, respectively. Although, increased [Ca2+]i or PKC activation each led to cell cycle entry, the subsequent response of these preactivated cells to complete activation with both signals was different: Cells pretreated with PMA alone for up to 24 hr could progress further to DNA synthesis after the addition of ionomycin. In contrast, cells activated with ionomycin alone, or those cultured without any stimulus, progressively lost the ability to show DNA synthesis after complete activation. The failure to progress to DNA synthesis in these two cases was, however, differentially regulated by the ability of these cells to produce IL-2 and to express IL-2R. Ionomycin-pretreated cells retained the ability to produce IL-2 but showed about 70% reduction in the numbers of IL-2R; whereas cells cultured without any stimulus lost the ability to produce IL-2 after subsequent complete activation, but showed lesser reduction in IL-2R expression.

Original languageEnglish (US)
Pages (from-to)483-496
Number of pages14
JournalCellular Immunology
Volume127
Issue number2
DOIs
StatePublished - 1990
Externally publishedYes

Fingerprint

lonomycin
Ionomycin
Interleukin-2 Receptors
Tetradecanoylphorbol Acetate
Interleukin-2
B-Lymphocytes
Protein Kinase C
Cell Cycle
DNA
Calcium Ionophores
Phorbol Esters
Cultured Cells
Blood Cells
Ions
Rabbits
Calcium

ASJC Scopus subject areas

  • Cell Biology
  • Immunology

Cite this

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title = "Molecular signals in B cell activation. I. Differential refractory effects of incomplete signaling by lonomycin or PMA relate to autocrine IL-2 production and IL-2R expression",
abstract = "The molecular signals required by resting (G0) B cells for the induction of cell cycle entry, IL-2 production, and high-affinity IL-2 receptor (IL-2R) expression were defined and the effects of incomplete activation signals on the subsequent response to complete signals were examined. Highly enriched rabbit peripheral blood B cells were activated with a calcium ionophore, ionomycin, and a protein kinase C (PKC) activating phorbol ester, phorbol myristate acetate (PMA). It was observed that cell cycle entry to early G1 was induced by either reagent acting alone, but both reagents were required to stimulate IL-2 production, IL-2R expression, and DNA synthesis. These effects of ionomycin and PMA were shown to be mediated by increased intracellular calcium ion concentration [Ca2+]i and PKC activation, respectively. Although, increased [Ca2+]i or PKC activation each led to cell cycle entry, the subsequent response of these preactivated cells to complete activation with both signals was different: Cells pretreated with PMA alone for up to 24 hr could progress further to DNA synthesis after the addition of ionomycin. In contrast, cells activated with ionomycin alone, or those cultured without any stimulus, progressively lost the ability to show DNA synthesis after complete activation. The failure to progress to DNA synthesis in these two cases was, however, differentially regulated by the ability of these cells to produce IL-2 and to express IL-2R. Ionomycin-pretreated cells retained the ability to produce IL-2 but showed about 70{\%} reduction in the numbers of IL-2R; whereas cells cultured without any stimulus lost the ability to produce IL-2 after subsequent complete activation, but showed lesser reduction in IL-2R expression.",
author = "Anand Lagoo and Chien-Te Tseng and Stewart Sell",
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T1 - Molecular signals in B cell activation. I. Differential refractory effects of incomplete signaling by lonomycin or PMA relate to autocrine IL-2 production and IL-2R expression

AU - Lagoo, Anand

AU - Tseng, Chien-Te

AU - Sell, Stewart

PY - 1990

Y1 - 1990

N2 - The molecular signals required by resting (G0) B cells for the induction of cell cycle entry, IL-2 production, and high-affinity IL-2 receptor (IL-2R) expression were defined and the effects of incomplete activation signals on the subsequent response to complete signals were examined. Highly enriched rabbit peripheral blood B cells were activated with a calcium ionophore, ionomycin, and a protein kinase C (PKC) activating phorbol ester, phorbol myristate acetate (PMA). It was observed that cell cycle entry to early G1 was induced by either reagent acting alone, but both reagents were required to stimulate IL-2 production, IL-2R expression, and DNA synthesis. These effects of ionomycin and PMA were shown to be mediated by increased intracellular calcium ion concentration [Ca2+]i and PKC activation, respectively. Although, increased [Ca2+]i or PKC activation each led to cell cycle entry, the subsequent response of these preactivated cells to complete activation with both signals was different: Cells pretreated with PMA alone for up to 24 hr could progress further to DNA synthesis after the addition of ionomycin. In contrast, cells activated with ionomycin alone, or those cultured without any stimulus, progressively lost the ability to show DNA synthesis after complete activation. The failure to progress to DNA synthesis in these two cases was, however, differentially regulated by the ability of these cells to produce IL-2 and to express IL-2R. Ionomycin-pretreated cells retained the ability to produce IL-2 but showed about 70% reduction in the numbers of IL-2R; whereas cells cultured without any stimulus lost the ability to produce IL-2 after subsequent complete activation, but showed lesser reduction in IL-2R expression.

AB - The molecular signals required by resting (G0) B cells for the induction of cell cycle entry, IL-2 production, and high-affinity IL-2 receptor (IL-2R) expression were defined and the effects of incomplete activation signals on the subsequent response to complete signals were examined. Highly enriched rabbit peripheral blood B cells were activated with a calcium ionophore, ionomycin, and a protein kinase C (PKC) activating phorbol ester, phorbol myristate acetate (PMA). It was observed that cell cycle entry to early G1 was induced by either reagent acting alone, but both reagents were required to stimulate IL-2 production, IL-2R expression, and DNA synthesis. These effects of ionomycin and PMA were shown to be mediated by increased intracellular calcium ion concentration [Ca2+]i and PKC activation, respectively. Although, increased [Ca2+]i or PKC activation each led to cell cycle entry, the subsequent response of these preactivated cells to complete activation with both signals was different: Cells pretreated with PMA alone for up to 24 hr could progress further to DNA synthesis after the addition of ionomycin. In contrast, cells activated with ionomycin alone, or those cultured without any stimulus, progressively lost the ability to show DNA synthesis after complete activation. The failure to progress to DNA synthesis in these two cases was, however, differentially regulated by the ability of these cells to produce IL-2 and to express IL-2R. Ionomycin-pretreated cells retained the ability to produce IL-2 but showed about 70% reduction in the numbers of IL-2R; whereas cells cultured without any stimulus lost the ability to produce IL-2 after subsequent complete activation, but showed lesser reduction in IL-2R expression.

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