T follicular regulatory cells: guardians of the germinal center?

Scandinavian Journal of Immunology
Cecilia Fahlquist Hagert, Søren E Degn

Abstract

It is a central tenet of the clonal selection theory, that lymphocyte repertoires are tolerized to self-antigens during their ontogeny. Germinal centers are the sites in secondary lymphoid tissues where B cells undergo affinity maturation and class-switching to produce high affinity antibodies. This process is crucial, both in our ability to mount protective humoral responses to infections and to vaccinations, but it is also involved in untoward reactions to self-antigens, which underlie autoimmunity. The process of affinity maturation poses a significant challenge to tolerance, as the random nature of somatic hypermutation can introduce novel reactivities. Therefore, it has been a long-standing idea that mechanisms must exist which limit the emergence of autoreactivity at the germinal center level. One of these mechanisms is the requirement for linked recognition, which imposes on B cells a dependence on centrally tolerant T follicular helper cells. However, as linked recognition can be bypassed by adduct formation of autoantigenic complexes, it has been an appealing notion that there should be an additional layer of dominant mechanisms regulating emergence of autoreactive specificities. About a decade ago, this notion was add...Continue Reading

References

Sep 24, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Hyung W LimChang H Kim
Jan 19, 2006·Blood·Dong-Mei ZhaoEthan M Shevach
Feb 29, 2008·The New England Journal of Medicine·Anisur Rahman, David A Isenberg
Jun 21, 2008·Nature Reviews. Immunology·Dario A A VignaliCreg J Workman
Nov 26, 2009·The Journal of Experimental Medicine·Tanja A SchwickertMichel C Nussenzweig
Jul 26, 2011·Nature Medicine·Michelle A LintermanCarola G Vinuesa
Oct 11, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ivonne WollenbergLuis Graca
Nov 29, 2011·Nature·Michael D RosenblumAbul K Abbas
Jan 10, 2012·Annual Review of Immunology·Gabriel D Victora, Michel C Nussenzweig
Dec 18, 2012·Nature Immunology·Peter T SageArlene H Sharpe
Jul 28, 2013·Science·Ziv ShulmanGabriel D Victora
Mar 5, 2014·The Journal of Experimental Medicine·Martin VaethFriederike Berberich-Siebelt
Mar 19, 2014·Nature Communications·Beatriz LeónAndré Ballesteros-Tato
May 9, 2014·Nature·Alexander D GitlinMichel C Nussenzweig
Jun 30, 2014·Nature Immunology·Masaki MiyazakiCornelis Murre
Aug 27, 2014·The Journal of Clinical Investigation·Mark J McCarron, Julien C Marie
Oct 28, 2014·The Journal of Clinical Investigation·Peter T SageArlene H Sharpe
Feb 3, 2015·Nature Immunology·Louise J McHeyzer-WilliamsMichael G McHeyzer-Williams
Jun 14, 2015·The Journal of Immunology : Official Journal of the American Association of Immunologists·Tessa DhaezeNiels Hellings
Jan 29, 2016·Nature Communications·Meryem AloulouMichelle A Linterman
Feb 26, 2016·Annual Review of Immunology·Carola G VinuesaIan C M MacLennan
Feb 26, 2016·Science·Jeroen M J TasGabriel D Victora
Apr 19, 2016·Immunological Reviews·Peter T Sage, Arlene H Sharpe
Feb 2, 2017·Annual Review of Immunology·Florian Weisel, Mark Shlomchik
Apr 22, 2017·Nature Communications·Ana Raquel MaceirasLuis Graca
Jul 13, 2017·Proceedings of the National Academy of Sciences of the United States of America·James Badger WingShimon Sakaguchi
Jul 16, 2017·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Bihua XuNiansheng Yang
Aug 26, 2017·Cell·Søren E DegnMichael C Carroll
Sep 25, 2017·Scientific Reports·Rashmi BankotiGislâine A Martins
Jan 31, 2018·The Journal of Experimental Medicine·Weiwei FuChen Dong
Mar 4, 2018·Nature Communications·Chen-Hao YehGarnett Kelsoe
Sep 11, 2018·Frontiers in Immunology·James B WingShimon Sakaguchi
Feb 2, 2019·The Journal of Experimental Medicine·Shenda HouPeter T Sage
Mar 16, 2019·Frontiers in Immunology·Paul-Gydéon Ritvo, David Klatzmann
May 17, 2019·The Journal of Clinical Endocrinology and Metabolism·Xinyu XuTao Yang

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Citations

Dec 30, 2020·Scandinavian Journal of Immunology·Petter Höglund
Aug 3, 2021·Journal of Immunology Research·Xin XiaShengjun Wang
Aug 22, 2021·Cellular & Molecular Immunology·Laura A HuppertJames C Lee

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Methods Mentioned

BETA
light microscopy

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