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

Proceedings of the National Academy of Sciences of the United States of America
Nadine BolligMichael Lohoff

Abstract

Follicular T-helper (T(FH)) 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 T(FH) 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 T(FH) key transcription factor B-cell lymphoma-6 and other T(FH)-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 T(FH) cells reconstituted GC formation, GC B-cell differentiation, and LN cell survival. In support of a T-cell intrinsic IRF4 activity, Irf4(-/-) T(FH) cell differentiation was not rescued by close neighborhood to transferred WT T(FH) cells. Together with its known B lineage-specific roles during plasma cell maturation and class switch, our study places IRF4 in ...Continue Reading

References

Aug 1, 1988·Infection and Immunity·M LohoffM Röllinghoff
Dec 22, 1999·The Journal of Experimental Medicine·S GuptaA B Pernis
Dec 6, 2000·The Journal of Experimental Medicine·P SchaerliB Moser
Apr 17, 2002·The Journal of Experimental Medicine·Jyothi RengarajanLaurie H Glimcher
Aug 22, 2002·Proceedings of the National Academy of Sciences of the United States of America·Michael LohoffTak W Mak
Jun 24, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Tatyana ChtanovaCharles R Mackay
Jul 14, 2004·The Journal of Experimental Medicine·Michael LohoffTak W Mak
Jan 20, 2005·The Journal of Experimental Medicine·Claire L LangrishDaniel J Cua
Feb 3, 2005·Nature Reviews. Immunology·Michael Lohoff, Tak W Mak
Aug 6, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Hisaya AkibaKo Okumura
Jun 13, 2006·Nature Immunology·Ulf KleinRiccardo Dalla-Favera
Aug 7, 2007·Nature Immunology·Anne BrüstleMichael Lohoff
Oct 4, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Nicole M HaynesJason G Cyster
Dec 7, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Vanessa L BryantStuart G Tangye
Apr 9, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Masashi WatanabeRyo Abe
Dec 18, 2008·Proceedings of the National Academy of Sciences of the United States of America·Magdalena HuberMichael Lohoff
Mar 3, 2009·Nature Immunology·R Lee ReinhardtRichard M Locksley
Apr 22, 2009·The Journal of Experimental Medicine·Irah L King, Markus Mohrs
Jul 25, 2009·Science·Roza I NurievaChen Dong
Feb 10, 2010·The Journal of Experimental Medicine·Michelle A LintermanCarola G Vinuesa
Feb 10, 2010·The Journal of Experimental Medicine·Dimitra ZotosDavid M Tarlinton
Aug 3, 2010·Immunology·Elizabeth C Nowak, Randolph J Noelle

❮ Previous
Next ❯

Citations

Oct 23, 2013·Immunology and Cell Biology·Hai QiJiacong Yan
Nov 6, 2013·Immunology and Cell Biology·Alvin Pratama, Carola G Vinuesa
Aug 28, 2013·Proceedings of the National Academy of Sciences of the United States of America·Friederike RaczkowskiMagdalena Huber
Apr 11, 2013·BMC Immunology·Tony SchountzJoseph Prescott
Mar 5, 2014·The Journal of Experimental Medicine·Martin VaethFriederike Berberich-Siebelt
Jun 1, 2014·Cellular and Molecular Life Sciences : CMLS·Laure Ysebrant de LendonckStanislas Goriely
Dec 17, 2014·Frontiers in Biology·Vipul Shukla, Runqing Lu
Jan 24, 2015·Biomolecules·David A Jackson, Sherine F Elsawa
May 9, 2014·Biochimica Et Biophysica Acta·Guang-Nian ZhaoHongliang Li
May 22, 2013·Current Opinion in Immunology·Youn Soo ChoiShane Crotty
Jun 4, 2013·Current Opinion in Immunology·Karen L Bunting, Ari M Melnick
Apr 5, 2013·Immunological Reviews·Vigo Heissmeyer, Katharina U Vogel
Feb 15, 2013·Immunological Reviews·Xindong LiuChen Dong
Dec 21, 2012·European Journal of Immunology·Alexander VisekrunaMagdalena Huber
May 2, 2014·European Journal of Immunology·Magdalena Huber, Michael Lohoff
Aug 16, 2014·Immunological Reviews·Subhash K Tripathi, Riitta Lahesmaa
Apr 14, 2016·Trends in Immunology·Julia Maul, Dirk Baumjohann
Oct 9, 2014·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Gwilym J Webb, Gideon M Hirschfield
Mar 4, 2014·Current Opinion in Immunology·Hai QiHu Yan
Nov 13, 2013·Autoimmunity·Inez RogatskyAlessandra B Pernis
Sep 18, 2013·International Reviews of Immunology·Consuelo OrtegaManuel Santamaría
Jun 23, 2015·Nature Immunology·Mélanie BruchardFrançois Ghiringhelli
Jun 30, 2015·Bioscience, Biotechnology, and Biochemistry·Wataru Ise
May 12, 2015·Journal of Immunology Research·Michela CroceSilvano Ferrini
Feb 7, 2015·Nature Reviews. Immunology·Nilushi S De Silva, Ulf Klein
Nov 7, 2015·PloS One·Michela ManniAlessandra B Pernis
Apr 10, 2016·European Journal of Immunology·Vicki AthanasopoulosCarola G Vinuesa
May 12, 2016·Molecular and Cellular Neurosciences·Heng LiRui-Sheng Duan
Feb 26, 2016·Annual Review of Immunology·Carola G VinuesaIan C M MacLennan
Jul 22, 2016·Immunology·Kaitlin A ReadKenneth J Oestreich

❮ Previous
Next ❯

Related Concepts

Related Feeds

B cells: Gene Expression

B lymphocytes are white blood cells that play a role in the adaptive immune system by secreting antibodies. Here is the latest research on gene expression in B cells.

B cell Differentiation

Depending on the signal received through the B cell receptor and other receptors, B cells differentiate into follicular or marginal zone B cells. Here is the latest research pertaining to this differentiation process.