---
title: "Tfh cell dysfunction linked to poor antibody responses after HBV vaccination"
id: "biorxiv-3-tfh-dysfunction-underlies-poor-responses-to-hbv-vaccination"
canonical_url: "https://medichelpline.com/clinical-feed/biorxiv-3-tfh-dysfunction-underlies-poor-responses-to-hbv-vaccination"
content_type: "clinical_feed_article"
specialty: "Infectious Disease"
source_name: "bioRxiv (Biomedical Preprints)"
source_url: "https://www.biorxiv.org/content/10.64898/2026.07.30.741822v1?rss=1"
published_at: "2026-08-04T12:00:00.000Z"
evidence_level: "Verified Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Tfh cell dysfunction linked to poor antibody responses after HBV vaccination
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/biorxiv-3-tfh-dysfunction-underlies-poor-responses-to-hbv-vaccination
- **Specialty:** [Infectious Disease](https://medichelpline.com/clinical-feed/infectious-disease.md)
- **Primary Source:** bioRxiv (Biomedical Preprints)
- **Source URL:** [Original Journal Publication](https://www.biorxiv.org/content/10.64898/2026.07.30.741822v1?rss=1)
- **Published At:** 2026-08-04T12:00:00.000Z
- **Evidence Rating:** Verified Feed
## Executive GIST (TL;DR)
- The study examined why individuals vary in antibody responses to Hepatitis B virus (**HBV**) vaccination by profiling immune responses in blood and vaccine-draining lymph nodes. - Researchers longitudinally followed 101 healthy adults receiving either de novo (n=59) or booster (n=42) HBV immunization and stratified participants into High (>100 mIU/mL) and Low (<100 mIU/mL) antibody responder groups. - Core needle biopsies of draining lymph nodes were obtained from 10 participants (High Responder n=6, Low Responder n=4) 10–21 days after the final vaccine dose for single-cell RNA sequencing with paired antigen receptor sequencing. - B cell receptor (BCR) repertoire analysis found convergent, semi-public clonotypes across unrelated participants and elevated somatic hypermutation (SHM) among these antigen-specific clones. - Transcriptomic profiling of germinal center (**GC-B**) cells revealed clear divergence: High Responders showed robust activation in both dark zone (DZ) and light zone (LZ) compartments with enrichment of **MYC** and **mTORC1** signaling, while Low Responders had a contracted LZ and a stalled GC B cell program. - High Responders had an expanded **T follicular helper (Tfh)** subset expressing **CXCL13**, **ICOS**, and **GNG4**, consistent with GC localization and B cell help capacity; receptor–ligand analysis suggested coordinated costimulatory networks enabling LZ GC-B cell licensing. - Low Responders exhibited a distinct Tfh transcriptional program: their **GNG4+ Tfh** showed aberrant inflammatory gene expression, associated with reduced specificity of **BCL6** regulon activity despite retention of canonical Tfh markers. - The authors conclude that variable HBV vaccine responsiveness correlates with altered transcriptional networks within the GNG4+ Tfh subset, providing a molecular framework for understanding poor vaccine responses. - No competing interests were declared. Funding sources reported include NIH grants and other foundations as listed in the source.
## Clinical Analysis & Structured Key Points
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Han M Chen 1 Department of Medicine, Division of Infectious Diseases and Immunology, NYU Grossman School of Medicine, New York CIty, NY.; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Han%2BM%2BChen%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Chen%20HM&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AHan%2BM%2BChen%2B) * [ORCID record for Han M Chen](http://orcid.org/0009-0001-8124-5792 "Open in new tab") Elizabeth Severa 1 Department of Medicine, Division of Infectious Diseases and Immunology, NYU Grossman School of Medicine, New York CIty, NY.; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Elizabeth%2BSevera%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Severa%20E&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AElizabeth%2BSevera%2B) Xiaomin Yao 1 Department of Medicine, Division of Infectious Diseases and Immunology, NYU Grossman School of Medicine, New York CIty, NY.; 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Yet the same vaccine may elicit durable protection in some and less durable responses in others. Antigen-specific antibody responses arise from germinal centers (GCs), where T follicular helper (Tfh) cells help cognate B cells undergo somatic hypermutation (SHM), affinity maturation to generate humoral protection and cellular immune memory. In humans, however, the mechanisms linking GC dynamics to downstream antibody output remain incompletely characterized. To identify the molecular and cellular event
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