Evolution of antigen-specific follicular helper T cell transcriptional programs across effector function and through to memory

Abstract Understanding how follicular helper T cells (TFH) regulate the specialization, maturation, and differentiation of adaptive B cell immunity is crucial for developing durable high-affinity immune protection. Using indexed-single cell molecular strategies, we reveal a skewed intra-clonal assortment of higher affinity TCR and the distinct molecular programming of the localized TFH compartment compared to emigrant conventional effector TH(ETH) cells. We find a temporal shift in BCR class switch which permits identification of inflammatory and anti-inflammatory modules of transcriptional programming that subspecialize TFH function before and during the germinal center (GC) reaction. Late collapse of this local primary GC reaction reveals a persistent post-GC TFH population which discloses a putative memory TFH program. These studies define specialized antigen-specific TFH transcriptional programs that progressively direct class-specific evolution of high-affinity B cell immunity and uncover the transcriptional program of a memory TFH population as the regulators of antigen recall.Graphical Abstract <jats:fig id="ufig1" position="float" orientation="portrait" fig-type="figure"><jats:graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="460841v1_ufig1" position="float" orientation="portrait" /></jats:fig>Summary Distinct inflammatory and anti-inflammatory antigen-specific TFH transcriptional programs regulate class-specific B cell maturation.Highlights <jats:list list-type="simple">- Skewed intra-clonal assortment of high affinity TCR into the TFH compartment- Significant temporal delay in anti-inflammatory IgG1 production- Inflammatory and anti-inflammatory transcriptional modules subspecialize TFH- Late GC collapse reveals a persisting post-GC putative memory TFH compartment.

Medienart:	Preprint

Erscheinungsjahr:	2023
Erschienen:	2023

Enthalten in:	bioRxiv.org - (2023) vom: 09. Jan. Zur Gesamtaufnahme - year:2023

Sprache:	Englisch

Beteiligte Personen:	Robinson, Amanda M. [VerfasserIn] Higgins, Brett W. [VerfasserIn] Shuparski, Andrew G. [VerfasserIn] Miller, Karen B. [VerfasserIn] McHeyzer-Williams, Louise J. [VerfasserIn] McHeyzer-Williams, Michael G. [VerfasserIn]

Links:	Volltext [kostenfrei]

Themen:	570 Biology

doi:	10.1101/2021.09.17.460841

funding:
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PPN (Katalog-ID):	XBI032614969