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

Academic Article

Abstract

  • 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 μ(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.
  • Published In

  • Immunity  Journal
  • Digital Object Identifier (doi)

    Author List

  • Randall TD; Heath AW; Santos-Argumedo L; Howard MC; Weissman IL; Lund FE
  • Start Page

  • 733
  • End Page

  • 742
  • Volume

  • 8
  • Issue

  • 6