Arrest of B lymphocyte terminal differentiation by CD40 signaling: mechanism for lack of antibody-secreting cells in germinal centers

Immunity. 1998 Jun;8(6):733-42. doi: 10.1016/s1074-7613(00)80578-6.


Despite extensive research, the role of CD40 signaling in B cell terminal differentiation remains controversial. Here we show that CD40 engagement arrests B cell differentiation prior to plasma cell formation. This arrest is manifested at a molecular level as a reduction in mRNA levels of secretory immunoglobulin gene products such as mu(s) and J chain as well as the loss of the transcriptional regulator BLIMP-1. Furthermore, the inhibition of B cell differentiation by CD40 engagement could not be overcome by either mitogens or cytokines, but could be reversed by antibodies that interfere with the CD40/gp39 interaction. These data suggest that secretory immunoglobulin is not produced by B cells that are actively engaged by gp39-expressing T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies / immunology
  • B-Lymphocytes / cytology
  • B-Lymphocytes / immunology*
  • CD40 Antigens / immunology*
  • CD40 Ligand
  • Cell Differentiation / immunology
  • Coculture Techniques
  • Germinal Center / cytology
  • Germinal Center / immunology*
  • Humans
  • Ligands
  • Membrane Glycoproteins / immunology
  • Mice
  • Mice, Inbred C57BL
  • Positive Regulatory Domain I-Binding Factor 1
  • Repressor Proteins*
  • Signal Transduction / immunology*
  • Transcription Factors / immunology


  • Antibodies
  • CD40 Antigens
  • Ligands
  • Membrane Glycoproteins
  • Prdm1 protein, mouse
  • Repressor Proteins
  • Transcription Factors
  • PRDM1 protein, human
  • CD40 Ligand
  • Positive Regulatory Domain I-Binding Factor 1