Toll-like receptor 4 signaling by follicular dendritic cells is pivotal for germinal center onset and affinity maturation

Immunity
Alexandre GarinMarie H Kosco-Vilbois

Abstract

Germinal centers (GCs) are specialized microenvironments where antigen-activated B cells undergo proliferation, immunoglobulin (Ig) class switch recombination, somatic hypermutation (SHM), and affinity maturation. Within GCs, follicular dendritic cells (FDCs) are key players in driving these events via direct interaction with GC B cells. Here, we provide in vivo evidence that FDCs express and upregulate Toll-like-receptor (TLR) 4 in situ during germinal center reactions, confirm that their maturation is driven by TLR4, and associate the role of FDC-expressed TLR4 with quantitative and qualitative affects of GC biology. In iterative cycles of predictions by in silico modeling subsequently verified by in vivo experiments, we demonstrated that TLR4 signaling modulates FDC activation, strongly impacting SHM and generation of Ig class-switched high-affinity plasma and memory B cells. Thus, our data place TLR4 in the heart of adaptive humoral immunity, providing further insight into mechanisms driving GCs arising in both health and disease.

References

Aug 22, 1996·Nature·J R NelsonD C Hinkle
Jun 9, 2001·Journal of Theoretical Biology·M Meyer-HermannM Or-Guil
Jul 9, 2003·Immunological Reviews·Ian C M MacLennanCarola G Vinuesa
Nov 18, 2005·Nature·Chandrashekhar Pasare, Ruslan Medzhitov
Feb 25, 2006·Cell·Shizuo AkiraOsamu Takeuchi
May 20, 2006·Nature·D NemazeeB Beutler
Oct 26, 2006·Nature Reviews. Immunology·Ann Marshak-Rothstein
Feb 6, 2007·Seminars in Immunology·Heung Kyu Lee, Akiko Iwasaki
Mar 16, 2007·Proceedings of the National Academy of Sciences of the United States of America·Glaucia C FurtadoSergio A Lira
Jul 20, 2007·Immunology and Cell Biology·Ashish Banerjee, Steve Gerondakis
Nov 28, 2007·The Journal of Experimental Medicine·Almut Meyer-BahlburgDavid J Rawlings
Dec 3, 2008·The Journal of Experimental Medicine·Marc Thilo FiggeMichael Meyer-Hermann
Mar 14, 2009·Trends in Immunology·Michael Meyer-HermannKai-Michael Toellner

❮ Previous
Next ❯

Citations

Jul 9, 2011·Nature Immunology·Stephen L Nutt, David M Tarlinton
Jun 19, 2013·Nature Immunology·Noelia A-GonzalezAntonio Castrillo
Nov 2, 2011·The Journal of Experimental Medicine·Xiaoming WangJason G Cyster
Nov 13, 2013·The Journal of Experimental Medicine·Jin-Shu HeMaria A Curotto de Lafaille
Jan 28, 2012·Science·Michael L Dustin, Michael Meyer-Hermann
Jul 29, 2011·Science Translational Medicine·Steven R WileyDarrick Carter
Nov 24, 2011·Clinical & Developmental Immunology·Alja Oblak, Roman Jerala
Dec 10, 2013·Trends in Immunology·Adriano AguzziNike Julia Krautler
May 28, 2014·The Journal of Experimental Medicine·Meryem JarjourMarc Bajénoff
Jul 28, 2013·Expert Review of Vaccines·Adele MountAdriana Baz Morelli
Dec 20, 2015·Glia·Hana JanovaUwe-Karsten Hanisch
Jan 20, 2016·CPT: Pharmacometrics & Systems Pharmacology·J CosgroveM Coles
Mar 27, 2012·Immunology·Edward P Browne
Oct 1, 2011·The Anatomical Record : Advances in Integrative Anatomy and Evolutionary Biology·Novica M MilićevićJurgen Westermann
Apr 10, 2013·European Journal of Immunology·Jianyong TangRonald N Germain
Mar 19, 2014·Journal of Internal Medicine·C Arama, M Troye-Blomberg
Feb 3, 2015·Cytometry. Part a : the Journal of the International Society for Analytical Cytology·Anna MedyukhinaMarc Thilo Figge
Aug 28, 2012·Immunity·Michael C Carroll, David E Isenman
Jul 21, 2010·Immunity·Jessy Deshane, David D Chaplin
Apr 17, 2012·Current Opinion in Immunology·Duncan B Sutherland, Sidonia Fagarasan
Dec 11, 2014·PloS One·Keith D MillerChristopher H Clegg
Sep 23, 2016·Immunity·Luka MesinGabriel D Victora
Oct 30, 2016·Trends in Immunology·Balthasar A HeestersMichael C Carroll
Dec 16, 2016·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sae-Hae KimYong-Suk Jang
Nov 1, 2017·The Journal of Experimental Medicine·Jan DudeckAnne Dudeck
Mar 16, 2019·Immunological Reviews·Ann M HabermanSteven M Kerfoot
Mar 16, 2019·The Journal of General Virology·Chen ChenLing Zhao
Apr 13, 2019·Immunological Reviews·Guilhem R ThierryMarc Bajenoff
Apr 13, 2019·Immunological Reviews·Christian Perez-ShibayamaBurkhard Ludewig
Jun 21, 2014·Nature Reviews. Immunology·Balthasar A HeestersMichael C Carroll
Aug 26, 2014·Nature Immunology·Viviana CremascoShannon J Turley
Nov 10, 2018·Frontiers in Immunology·Marisa StebeggLuis Graca
Mar 16, 2013·Physical Biology·Sana RaoofEugene I Shakhnovich
Sep 2, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Johan MattssonNils Y Lycke
Jun 2, 2020·Frontiers in Immunology·Kristy FuConstantinos Petrovas
Apr 18, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Xiaoming WangJason G Cyster

❮ 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.

Avian Influenza: Innate Immune Adjuvant

Adjuvants systems that are added to vaccines against avian influenza have be explored to enhance the innate immune system response against the virus. Here is the latest research on avian influenza and the innate immune adjuvant.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

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.

Avian Influenza: Innate Immune Adjuvant (ASM)

Adjuvants systems that are added to vaccines against avian influenza have be explored to enhance the innate immune system response against the virus. Here is the latest research on avian influenza and the innate immune adjuvant.