CAMP-independent effects of cholera toxin on B cell activation: III. Cholera toxin a subunit-mediated ADP-ribosylation acts synergistically with lonomycin or IL-4 to induce B cell proliferation

Mark L. Francis, Lan Okazaki, Joel Moss, Alexander Kurosky, Ligia M T Pecanha, James J. Mond

Research output: Contribution to journalArticle

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Abstract

To investigate whether ADP-ribosylation of proteins by cholera toxin could influence B cell activation, B cells were incubated with the A subunit of cholera toxin, lonomycin acted synergistically to induce B cell proliferation with the A subunit of cholera toxin but not with cAMP-enhancing agents or with the B subunit of cholera toxin, suggesting that the synergistic effect of the A subunit was mediated via ADP-ribosylation and not via cAMP elevations or ganglioside GM1 binding. Indeed, inhibitors of ADP-ribosylation blocked the synergistic effect. Unlike anti-lg, B cell proliferation stimulated by LPS or by the combination of the A subunit and ionomycin was observed in protein kinase C (PKC)-depleted B cells. However, neither the A subunit nor ionomycin enhanced B cell proliferation stimulated by low dose LPS, suggesting that the A subunit plus ionomycin stimulated an activation pathway distinct from the LPS-stimulated pathway. Additionally, unlike LPS, the A subunit plus ionomycin did not stimulate B cells in vitro to secrete Ig. IL-4 acted synergistically with the A subunit to induce B cell proliferation to the same extent as it did with anti-lg; unlike the anti-lg plus IL-4 synergy, however, the A subunit plus IL-4mediated synergy persisted in PKC-depleted B cells. Taken together, our data suggest that cholera toxin A subunitcatalyzed ADP-ribosylation modifies a non-Gs protein involved in the activation of B cells, either through a novel pathway or at a point distal to the activation of PKC along the anti-lg-stimulated pathway.

Original languageEnglish (US)
Pages (from-to)4956-4964
Number of pages9
JournalJournal of Immunology
Volume154
Issue number10
StatePublished - 1995
Externally publishedYes

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lonomycin
Cholera Toxin
Interleukin-4
Adenosine Diphosphate
B-Lymphocytes
Cell Proliferation
Ionomycin
Protein Kinase C
G(M1) Ganglioside

ASJC Scopus subject areas

  • Immunology

Cite this

CAMP-independent effects of cholera toxin on B cell activation : III. Cholera toxin a subunit-mediated ADP-ribosylation acts synergistically with lonomycin or IL-4 to induce B cell proliferation. / Francis, Mark L.; Okazaki, Lan; Moss, Joel; Kurosky, Alexander; Pecanha, Ligia M T; Mond, James J.

In: Journal of Immunology, Vol. 154, No. 10, 1995, p. 4956-4964.

Research output: Contribution to journalArticle

Francis, Mark L. ; Okazaki, Lan ; Moss, Joel ; Kurosky, Alexander ; Pecanha, Ligia M T ; Mond, James J. / CAMP-independent effects of cholera toxin on B cell activation : III. Cholera toxin a subunit-mediated ADP-ribosylation acts synergistically with lonomycin or IL-4 to induce B cell proliferation. In: Journal of Immunology. 1995 ; Vol. 154, No. 10. pp. 4956-4964.
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