Loss of CD154 impairs the Th2 extrafollicular plasma cell response but not early T cell proliferation and interleukin-4 induction

Immunology. 2004 Oct;113(2):187-93. doi: 10.1111/j.1365-2567.2004.01951.x.


Ligation of CD40 by CD4 T cells through CD154 is key both to germinal centre induction and follicular T-dependent Ig class switching, but its requirement for aspects of T cell priming and extrafollicular antibody responses is less clear. Here comparison of the T helper (Th) type 2 response in lymph nodes from wild-type mice and CD154-deficient mice after immunization with alum-precipitated antigen reveals selective effects of this immunodeficiency. The timing and magnitude of the early interleukin (IL)-4 induction and proliferation in T cells of the T zone were unaltered by CD154 deficiency. As expected, germinal centres were not induced. Additionally the T-dependent extrafollicular antibody response, which initially requires T cell help but expands without further T cell involvement, was severely curtailed. The median number of extrafollicular antigen-specific plasma cells was 370-fold lower in CD154-deficient mice. Of these plasma cells the median proportion that had switched to IgG1 was <5%, while in wild-type mice the proportion was 89%. Surprisingly, some CD154-deficient lymph nodes showed substantial switching to IgG1. Commensurately, increases in gamma1 germline transcripts and Blimp-1 mRNA were observed, albeit significantly lower than in controls, but activation-induced cytidine deaminase mRNA was undetectable in CD154-deficient mice. These experiments demonstrate that the acquisition of some T cell priming characteristics can be CD154-independent; in contrast, T-dependent extrafollicular responses require CD154. Thus functional CD154 ligation during the first encounter of T cells and B cells in the T zone is critical for follicular and extrafollicular antibody responses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibody Formation
  • CD40 Antigens / immunology
  • CD40 Ligand / immunology*
  • Cell Differentiation / immunology
  • Cytidine Deaminase / immunology
  • Enzyme-Linked Immunosorbent Assay / methods
  • Germinal Center / immunology
  • Immunoglobulin G / immunology
  • Interleukin-4 / immunology*
  • Lymphocyte Activation / immunology
  • Mice
  • Mice, Inbred Strains
  • Positive Regulatory Domain I-Binding Factor 1
  • RNA, Messenger / genetics
  • Repressor Proteins / immunology
  • Reverse Transcriptase Polymerase Chain Reaction / methods
  • Th2 Cells / immunology*
  • Transcription Factors / immunology


  • CD40 Antigens
  • Immunoglobulin G
  • Prdm1 protein, mouse
  • RNA, Messenger
  • Repressor Proteins
  • Transcription Factors
  • CD40 Ligand
  • Interleukin-4
  • Positive Regulatory Domain I-Binding Factor 1
  • Cytidine Deaminase