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

Immunology
Adam F CunninghamK M Toellner

Abstract

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 signific...Continue Reading

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Citations

May 3, 2012·Nature Reviews. Rheumatology·Joseph E Craft
Jun 3, 2009·Proceedings of the National Academy of Sciences of the United States of America·Cristina Gil-CruzAdam F Cunningham
Sep 9, 2010·Expert Review of Vaccines·Katrina L Randall
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Apr 17, 2012·Immunological Reviews·Jason S WeinsteinJoe Craft
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Nov 18, 2014·Frontiers in Immunology·Adam F CunninghamIan R Henderson
Aug 31, 2016·Nature Reviews. Immunology·Hai Qi
Mar 16, 2019·Immunological Reviews·Wenzhi Song, Joe Craft
Jan 28, 2006·Blood·Giorgio CattorettiGerald Niedobitek
Jul 2, 2020·The Journal of Experimental Medicine·Verónica Delgado-BenitoMichela Di Virgilio
Nov 20, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jennifer L MarshallAdam F Cunningham
Aug 22, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·James P HewitsonAdrian P Mountford
May 4, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Adam F CunninghamIan C M MacLennan
Dec 31, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Victoria GorbachevaAnna Valujskikh
Nov 16, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Adriana Flores-LangaricaAdam F Cunningham

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