Antigen and helper T lymphocytes activate B lymphocytes by distinct signaling pathways

Kazuyoshi Kawakami, David C. Parker

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

Resting murine B lymphocytes can be induced to proliferate by cross‐linking membrane immunoglobulin, the antigen receptor, or by contact with activated helper T lymphocytes in the absence of a signal through membrane immunoglobulin. Little is known about the molecular nature of contact‐dependent T cell help. To determine whether helper T cells activate B cells through different signal transduction and second messenger pathways from those used by membrane immunoglobulin, the effects of drugs which block activation of B cells through membrane immunoglobulin were measured on B cell activation by contact with anti‐CD3‐activated and fixed T helper cells. Cyclosporin A, phorbol esters added at the time of activation, and cAMP agonists all block activation of B cells through membrane immunoglobulin at concentrations at least 100‐fold lower than those necessary to block B cell activation by contact with activated Th1 or Th2 helper T cells. Depletion of protein kinase C by pretreatment of B cells with phorbol ester inhibits the proliferative response to anti‐immunoglobulin but not the response to contact with activated T cells. The B cell response to lipopolysaccharide is intermediate in sensitivity to cyclosporin A and cAMP agonists, and resembles the response to activated T cells in resistance to phorbol esters and protein kinase C depletion. Various protein kinase inhibitors did not distinguish among these B cell activation pathways, except for the tyrosine kinase inhibitor, herbimycin A, which inhibited anti‐immunoglobulin responses at 3‐ to 5‐fold lower concentrations.

Original languageEnglish (US)
Pages (from-to)77-84
Number of pages8
JournalEuropean Journal of Immunology
Volume23
Issue number1
DOIs
StatePublished - Jan 1993

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Keywords

  • B cell activation
  • Helper T lymphocytes
  • Signaling pathways

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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