Signaling via major histocompatibility complex class II molecules and antigen receptors enhances the B cell response to gp39/CD40 ligand

Gail A. Bishop, Wendy D. Warren, Michael T. Berton

Research output: Contribution to journalArticlepeer-review

56 Scopus citations

Abstract

Activated T cells induce proliferation and differentiation of resting B cells in vitro through their CD40 molecules and lymphokine receptors. However, despite constitutive B cell expression of CD40 and lymphokine receptors, widespread nonspecific polyclonal B cell activation by activated T cells is seldom observed in vivo. The present study was designed to test the hypothesis that signals delivered via the B cell antigen (Ag) receptor (membrane immunoglobulin, mIg) and major histocompatibility complex (MHC) class II molecules enhance B cell responsiveness to CD40‐mediated signals, providing specificity to the Ag‐nonspecific, MHC‐unrestricted CD40 signal. To test this hypothesis, both an Ag‐specific mouse B cell clone CH12.LX, and freshly isolated resting splenic B cells were cultured with either soluble or membrane‐bound forms of the T cell ligand for CD40 (CD40L), in the presence or absence of additional signals provided by Ag or anti‐IgM, interleukin‐4, and class II‐specific monoclonal antibody (mAb). Differentiation of CH12.LX cells and proliferation of splenic B cells in response to both forms of CD40L was greatly enhanced by exposure to mIg‐mediated signals, with greatest enhancement seen when cells were cultured with Ag prior to receiving other signals. Response to CD40L was further enhanced by concurrent culture with class II‐specific, but not class I‐specific mAb. Enhancement was greatest at limiting concentrations of CD40L. The ability of class II MHC‐mediated signals to enhance Ag‐specific B cell responsiveness to CD40‐mediated signaling may selectively promote the activation of B cell clones capable of cognate interactions with helper T cells.

Original languageEnglish (US)
Pages (from-to)1230-1238
Number of pages9
JournalEuropean Journal of Immunology
Volume25
Issue number5
DOIs
StatePublished - May 1995

Keywords

  • Activation
  • B lymphocyte
  • CD40
  • Class II
  • Immunoglobulin

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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