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

TitleTranscription factor IRF4 determines germinal center formation through follicular T-helper cell differentiation
Authors
KeywordsInducible costimulator
Apoptosis
Interleukin-21
CXC-chemokine receptor 5
Issue Date2012
Citation
Proceedings of the National Academy of Sciences of the United States of America, 2012, v. 109, n. 22, p. 8664-8669 How to Cite?
AbstractFollicular 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 Peyer's patches of naive Irf4 -/-mice. Accordingly, CD4+ T cells within the LNs and Peyer's patches failed to express the TFH key transcription factor B-cell lymphoma- 6 and other TFH-related molecules. During chronic leishmaniasis, the draining Irf4-/- LNs disappeared because of massive cell death. Adoptive transfer of WT CD4+ T cells or few L. major 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 T-cell-dependent antigens.
Persistent Identifierhttp://hdl.handle.net/10722/291348
ISSN
2023 Impact Factor: 9.4
2023 SCImago Journal Rankings: 3.737
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorBollig, Nadine-
dc.contributor.authorBrus̈tle, Anne-
dc.contributor.authorKellner, Kerstin-
dc.contributor.authorAckermann, Waltraud-
dc.contributor.authorAbass, Elfadil-
dc.contributor.authorRaifer, Hartmann-
dc.contributor.authorCamara, Bärbel-
dc.contributor.authorBrendel, Cornelia-
dc.contributor.authorGiel, Gavin-
dc.contributor.authorBothur, Evita-
dc.contributor.authorHuber, Magdalena-
dc.contributor.authorPaul, Christoph-
dc.contributor.authorElli, Alexandra-
dc.contributor.authorKroczek, Richard A.-
dc.contributor.authorNurieva, Roza-
dc.contributor.authorDong, Chen-
dc.contributor.authorJacob, Ralf-
dc.contributor.authorMak, Tak W.-
dc.contributor.authorLohoff, Michael-
dc.date.accessioned2020-11-17T14:54:10Z-
dc.date.available2020-11-17T14:54:10Z-
dc.date.issued2012-
dc.identifier.citationProceedings of the National Academy of Sciences of the United States of America, 2012, v. 109, n. 22, p. 8664-8669-
dc.identifier.issn0027-8424-
dc.identifier.urihttp://hdl.handle.net/10722/291348-
dc.description.abstractFollicular 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 Peyer's patches of naive Irf4 -/-mice. Accordingly, CD4+ T cells within the LNs and Peyer's patches failed to express the TFH key transcription factor B-cell lymphoma- 6 and other TFH-related molecules. During chronic leishmaniasis, the draining Irf4-/- LNs disappeared because of massive cell death. Adoptive transfer of WT CD4+ T cells or few L. major 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 T-cell-dependent antigens.-
dc.languageeng-
dc.relation.ispartofProceedings of the National Academy of Sciences of the United States of America-
dc.subjectInducible costimulator-
dc.subjectApoptosis-
dc.subjectInterleukin-21-
dc.subjectCXC-chemokine receptor 5-
dc.titleTranscription factor IRF4 determines germinal center formation through follicular T-helper cell differentiation-
dc.typeArticle-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1073/pnas.1205834109-
dc.identifier.pmid22552227-
dc.identifier.pmcidPMC3365194-
dc.identifier.scopuseid_2-s2.0-84861872906-
dc.identifier.volume109-
dc.identifier.issue22-
dc.identifier.spage8664-
dc.identifier.epage8669-
dc.identifier.eissn1091-6490-
dc.identifier.isiWOS:000304881700063-
dc.identifier.issnl0027-8424-

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