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Loss of CD154 impairs the Th2 extrafollicular plasma cell response but not early T cell proliferation and interleukin‐4 induction
Author(s) -
Cunningham Adam F.,
Serre Karine,
Mohr Elodie,
Khan Mahmood,
Toellner KaiMichael
Publication year - 2004
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.2004.01951.x
Subject(s) - cd154 , biology , germinal center , cd40 , plasma cell , priming (agriculture) , t cell , immunology , immune system , antibody , microbiology and biotechnology , b cell , cytotoxic t cell , biochemistry , botany , germination , in vitro
Summary 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 γ1 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.