B cells activated via CD40 and IL-4 undergo a division burst but require continued stimulation to maintain division, survival and differentiation

Eur J Immunol. 2001 Apr;31(4):1150-9. doi: 10.1002/1521-4141(200104)31:4<1150::aid-immu1150>3.0.co;2-v.


T cell stimulation of B cell proliferation during T-B collaboration requires membrane-bound stimulatory ligands, such as CD40 ligand and the secretion of soluble cytokines, such as IL-4. Nevertheless, it remains unclear whether T cell contact is required to provoke each consecutive B cell division, or whether B cells divide in a T cell-free burst following the initial stimulation. To test this, naive B cells were cultured with anti-CD40 monoclonal antibody (mAb) and IL-4 and, after various times, these stimuli were removed and the cells re-cultured with or without further stimulation. Following stimulus removal, B cells were able to continue proliferating, with the size of the B cell burst dependent on the strength of the initial anti-CD40 mAb stimulus. Furthermore, in the absence of activating signals from anti-CD40 and/or IL-4, re-cultured B cells died rapidly. In addition, B cells undergoing a stimulus-free division burst could switch to IgG1. Thus, maximal B cell proliferation, differentiation and survival may require continued, although not necessarily consecutive, cognate interactions with T cells. These results suggest that antigen persistence and T cell help are necessary to sustain B cell proliferation and differentiation in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology
  • B-Lymphocytes / cytology*
  • B-Lymphocytes / immunology*
  • CD40 Antigens / immunology*
  • CD40 Ligand / immunology
  • Cell Differentiation
  • Cell Division
  • Cell Survival
  • Cells, Cultured
  • Dose-Response Relationship, Immunologic
  • Female
  • Immunoglobulin Class Switching
  • Immunoglobulin G / immunology
  • Interleukin-4 / antagonists & inhibitors
  • Interleukin-4 / immunology*
  • Lymphocyte Activation*
  • Lymphocyte Count
  • Male
  • Mice
  • Mice, Inbred CBA
  • Signal Transduction
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology


  • Antibodies, Monoclonal
  • CD40 Antigens
  • Immunoglobulin G
  • CD40 Ligand
  • Interleukin-4