Engagement of CD40 lowers the threshold for activation of resting B cells via antigen receptor

Eur J Immunol. 1993 May;23(5):1165-8. doi: 10.1002/eji.1830230528.

Abstract

Cross-linking of surface Ig (sIg) on resting B cells can generate intracellular signals; however, for T-dependent antigens to promote growth and differentiation additional surface receptors must be engaged. Ligation of CD40 can stimulate B cell proliferation in the presence of interleukin-4. A recently identified counterstructure for CD40 is found on T helper cells and is believed to represent the cognate ligand for B cell activation. This study investigates the role of CD40 as an accessory molecule in sIg-dependent B cell activation. Simultaneous ligation of sIg and CD40 by monoclonal antibodies (mAb) in the presence of mouse L cells which express human Fc gamma receptor type II (Fc gamma RII-L cells) results in potent stimulation of small resting B cells. When CD40 is co-ligated, picomolar concentrations of mouse IgG1 anti-mu, and anti-delta mAb can stimulate B cell proliferation. This requires interaction of the anti-Ig mAb with the Fc gamma RII-L cells: a mouse IgG2a anti-mu mAb which is not recognized by Fc gamma RII, was > or = 1000-fold less effective. These findings suggest a mechanism for B cell activation whereby engagement of T cells via CD40 and its cognate ligand provides potent enhancement of signals delivered through sIg. Based on these observations, models for the activation of B cells by T-dependent antigens are presented.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / immunology
  • Antigens, CD / physiology*
  • Antigens, Differentiation, B-Lymphocyte / physiology*
  • B-Lymphocytes / immunology*
  • CD40 Antigens
  • Humans
  • Interleukin-4 / pharmacology
  • Lymphocyte Activation*
  • Receptors, Antigen / physiology*
  • Receptors, Antigen, B-Cell / immunology
  • Receptors, IgG / physiology
  • T-Lymphocytes / immunology

Substances

  • Antibodies, Monoclonal
  • Antigens, CD
  • Antigens, Differentiation, B-Lymphocyte
  • CD40 Antigens
  • Receptors, Antigen
  • Receptors, Antigen, B-Cell
  • Receptors, IgG
  • Interleukin-4