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Bollig, Nadine; Brüstle, Anne; Kellner, Kerstin; Ackermann, Waltraud; Abass, Elfadil; Raifer, Hartmann; Camara, Bärbel; Brendel, Cornelia; Giel, Gavin; Bothur, Evita; Huber, Magdalena; Paul, Christoph; Elli, Alexandra; Kroczek, Richard A.; Nurieva, Roza; Dong, Chen; Jacob, Ralf; Mak, Tak W.; Lohoff, Michael

Transcription factor IRF4 determines germinal center formation through follicular T-helper cell differentiation

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  • Media type: E-Article
  • Title: Transcription factor IRF4 determines germinal center formation through follicular T-helper cell differentiation
  • Contributor: Bollig, Nadine; Brüstle, Anne; Kellner, Kerstin; Ackermann, Waltraud; Abass, Elfadil; Raifer, Hartmann; Camara, Bärbel; Brendel, Cornelia; Giel, Gavin; Bothur, Evita; Huber, Magdalena; Paul, Christoph; Elli, Alexandra; Kroczek, Richard A.; Nurieva, Roza; Dong, Chen; Jacob, Ralf; Mak, Tak W.; Lohoff, Michael
  • imprint: Proceedings of the National Academy of Sciences, 2012
  • Published in: Proceedings of the National Academy of Sciences
  • Language: English
  • DOI: 10.1073/pnas.1205834109
  • ISSN: 0027-8424; 1091-6490
  • Keywords: Multidisciplinary
  • Origination:
  • Footnote:
  • Description: <jats:p>Follicular T-helper (T<jats:sub>FH</jats:sub>) cells cooperate with GL7<jats:sup>+</jats:sup>CD95<jats:sup>+</jats:sup>germinal center (GC) B cells to induce antibody maturation. Herein, we identify the transcription factor IRF4 as a T-cell intrinsic precondition for T<jats:sub>FH</jats:sub>cell differentiation and GC formation. After immunization with protein or infection with the protozoon<jats:italic>Leishmania major</jats:italic>, draining lymph nodes (LNs) of IFN-regulatory factor-4 (<jats:italic>Irf4<jats:sup>−/−</jats:sup></jats:italic>) mice lacked GCs and GC B cells despite developing normal initial hyperplasia. GCs were also absent in Peyer’s patches of naive<jats:italic>Irf4<jats:sup>−/−</jats:sup></jats:italic>mice. Accordingly, CD4<jats:sup>+</jats:sup>T cells within the LNs and Peyer’s patches failed to express the T<jats:sub>FH</jats:sub>key transcription factor B-cell lymphoma-6 and other T<jats:sub>FH</jats:sub>-related molecules. During chronic leishmaniasis, the draining<jats:italic>Irf4<jats:sup>−/−</jats:sup></jats:italic>LNs disappeared because of massive cell death. Adoptive transfer of WT CD4<jats:sup>+</jats:sup>T cells or few<jats:italic>L. major</jats:italic>primed WT T<jats:sub>FH</jats:sub>cells reconstituted GC formation, GC B-cell differentiation, and LN cell survival. In support of a T-cell intrinsic IRF4 activity,<jats:italic>Irf4<jats:sup>−/−</jats:sup></jats:italic>T<jats:sub>FH</jats:sub>cell differentiation was not rescued by close neighborhood to transferred WT T<jats:sub>FH</jats:sub>cells. Together with its known B lineage-specific roles during plasma cell maturation and class switch, our study places IRF4 in the center of antibody production toward T-cell–dependent antigens.</jats:p>
  • Access State: Open Access