Toll-like receptor 9 antagonizes antibody affinity maturation

Nature Immunology
Munir AkkayaSusan K Pierce

Abstract

Key events in T cell-dependent antibody responses, including affinity maturation, are dependent on the B cell's presentation of antigen to helper T cells at critical checkpoints in germinal-center formation in secondary lymphoid organs. Here we found that signaling via Toll-like receptor 9 (TLR9) blocked the ability of antigen-specific B cells to capture, process and present antigen and to activate antigen-specific helper T cells in vitro. In a mouse model in vivo and in a human clinical trial, the TLR9 agonist CpG enhanced the magnitude of the antibody response to a protein vaccine but failed to promote affinity maturation. Thus, TLR9 signaling might enhance antibody titers at the expense of the ability of B cells to engage in germinal-center events that are highly dependent on B cells' capture and presentation of antigen.

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Citations

Jul 10, 2019·Nature Immunology·Kihyuck KwakSusan K Pierce
Sep 26, 2019·Immunological Reviews·Prasida HollaSusan K Pierce
Dec 15, 2019·Nature Reviews. Immunology·Munir AkkayaSusan K Pierce
Apr 19, 2020·Immunological Reviews·Zhaolin Hua, Baidong Hou
Apr 8, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jasper RipOdilia B J Corneth
Jan 11, 2019·Science Translational Medicine·James G BeesonMichelle J Boyle
May 20, 2020·Frontiers in Immunology·Michael H ZhangGregory L Szeto
Apr 25, 2020·Viral Immunology·Jonathan H LamNicole Baumgarth
Feb 15, 2019·Frontiers in Immunology·Jasper RipOdilia B J Corneth
Feb 4, 2021·IScience·Juan Carlos Yam-PucKai-Michael Toellner
Mar 5, 2021·The Journal of Experimental Medicine·Christine S HoppPeter D Crompton
Apr 10, 2020·Cell Host & Microbe·P J KlasseJohn P Moore
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Jul 20, 2021·Frontiers in Immunology·Anoma NellorePaige M Porrett
Jul 23, 2021·The Journal of Experimental Medicine·Cecilia B CavazzoniAndre M Vale

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Datasets Mentioned

BETA
AAA48943.1
PRJNA422889

Methods Mentioned

BETA
flow cytometry
transgenic
transmission electron microscopy
fluorescence microscopy
PMS
RNA-seq
chips
transfection
fluorescence imaging
transmission

Clinical Trials Mentioned

NCT00320658

Software Mentioned

Cufflinks suite
Imaris
Amira for Biosciences
Metamorph
SerialEM
BIAevaluation
FastX Tool Kit
Image Pro Plus
Flowjo
Tophat2

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