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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: National Academy of Sciences, 2012
  • Published in: Proceedings of the National Academy of Sciences of the United States of America
  • Language: English
  • ISSN: 0027-8424
  • Origination:
  • Footnote:
  • Description: <p>Follicular T-helper (TFH) cells cooperate with GL7⁺ CD95⁺ germinal center (GC) B cells to induce antibody maturation. Herein, we identify the transcription factor IRF4 as a T-cell intrinsic precondition for TFH cell differentiation and GC formation. After immunization with protein or infection with the protozoon Leishmania major, draining lymph nodes (LNs) of IFN-regulatory factor-4 (Irf4-/-) mice lacked GCs and GC B cells despite developing normal initial hyperplasia. GCs were also absent in Peyeras patches of naive Irf4-/- mice. Accordingly, CD4⁺ T cells within the LNs and Peyeras patches failed to express the TFH key transcription factor B-cell lymphoma-6 and other TFH-related molecules. During chronic leishmaniasis, the draining IrfA-/- LNs disappeared because of massive cell death. Adoptive transfer of WT CD4⁺ T cells or few L mayor primed WT TFH cells reconstituted GC formation, GC B-cell differentiation, and LN cell survival. In support of a T-cell intrinsic IRF4 activity, Irf4-/- TFH cell differentiation was not rescued by close neighborhood to transferred WT TFH 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 Tcell-dependeht antigens.</p>
  • Access State: Open Access