---
title: "Autoantibody-driven priming of spontaneous germinal centers by autoreactive B cells"
id: "biorxiv-20-antibody-dependent-priming-of-spontaneous-germinal-centers-by-autoreactive-b"
canonical_url: "https://medichelpline.com/clinical-feed/biorxiv-20-antibody-dependent-priming-of-spontaneous-germinal-centers-by-autoreactive-b"
content_type: "clinical_feed_article"
specialty: "General"
source_name: "bioRxiv (Biomedical Preprints)"
source_url: "https://www.biorxiv.org/content/10.64898/2026.08.27.745373v1?rss=1"
published_at: "2026-09-01T12:00:00.000Z"
evidence_level: "Verified Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Autoantibody-driven priming of spontaneous germinal centers by autoreactive B cells
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/biorxiv-20-antibody-dependent-priming-of-spontaneous-germinal-centers-by-autoreactive-b
- **Specialty:** [General](https://medichelpline.com/clinical-feed/general.md)
- **Primary Source:** bioRxiv (Biomedical Preprints)
- **Source URL:** [Original Journal Publication](https://www.biorxiv.org/content/10.64898/2026.08.27.745373v1?rss=1)
- **Published At:** 2026-09-01T12:00:00.000Z
- **Evidence Rating:** Verified Feed
## Executive GIST (TL;DR)
- Autoreactive **B cells** can prime formation of spontaneous **germinal centers (GCs)** and break tolerance in otherwise wild-type B cells through a mechanism that does not require cognate T cell help. - The study used the 564Igi mixed chimera model to track how a single autoreactive B cell clone influences systemic autoimmunity in vivo. - B cell-intrinsic signaling via **TLR7** was necessary for spontaneous GC formation, indicating an innate-sensing requirement within autoreactive B cells themselves. - Deletion of classic B cell antigen-presentation or costimulatory molecules — MHC class II, CD40, or CD80/86 — on the GC-priming 564Igi B cells did not prevent spontaneous GCs, arguing against a requirement for B cell-intrinsic cognate T cell interactions. - CRISPR-mediated deletion of Prdm1 (encoding **BLIMP-1**) in 564Igi B cells abolished spontaneous GC formation, implicating differentiation to antibody-secreting states and **autoantibody** production as the primary driver of the process. - The data support a feed-forward model in which autoantibodies generated by autoreactive clones promote systemic propagation of autoimmunity independent of B cell antigen presentation. - The authors conclude that autoantibody production, rather than B cell presentation to T cells, can initiate and sustain spontaneous GCs in this model. Details on experimental protocols, sample sizes, and additional controls were not reported in the source preview.
## Clinical Analysis & Structured Key Points
Antibody-dependent priming of spontaneous germinal centers by autoreactive B cells | bioRxiv Skip to main content New Results Antibody-dependent priming of spontaneous germinal centers by autoreactive B cells Danny Kim , View ORCID Profile Kristy Chiang , View ORCID Profile Andrea D Largent , Ragan A Pitner , View ORCID Profile Sivasankaran Munusamy Ponnan , View ORCID Profile Brock J McKinney , View ORCID Profile Richard G James , View ORCID Profile David J Rawlings , View ORCID Profile Shaun W Jackson doi: https://doi.org/10.64898/2026.08.27.745373 Danny Kim Seattle Children's Research Institute Find this author on Google Scholar Find this author on PubMed Search for this author on this site Kristy Chiang Seattle Children's Research Institute Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Kristy Chiang Andrea D Largent Seattle Children's Research Institute Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Andrea D Largent Ragan A Pitner Seattle Children's Research Institute Find this author on Google Scholar Find this author on PubMed Search for this author on this site Sivasankaran Munusamy Ponnan Seattle Children's Research Institute Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Sivasankaran Munusamy Ponnan Brock J McKinney Seattle Children's Research Institute Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Brock J McKinney Richard G James Seattle Children's Research Institute Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Richard G James David J Rawlings Seattle Children's Research Institute Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for David J Rawlings Shaun W Jackson Seattle Children's Research Institute Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Shaun W Jackson For correspondence: shaun.jackson{at}seattlechildrens.org Abstract Info/History Metrics Preview PDF Abstract Autoreactive germinal centers (GCs) are central to autoimmune pathogenesis, yet the mechanisms by which single autoreactive B cell clones prime systemic autoimmunity remain unclear. Using the 564Igi mixed chimera model, we demonstrate that autoreactive 564Igi B cells break tolerance in wild-type B cells through an unexpected mechanism independent of cognate T cell interactions. While B cell-intrinsic TLR7 signaling was essential for spontaneous GC formation, deletion of MHC class II, CD40, or CD80/86 on GC-priming 564Igi B cells failed to prevent GCs. Instead, CRISPR-mediated deletion of Prdm1 (encoding BLIMP-1) in 564Igi B cells ablated spontaneous GCs, implicating autoantibody production as the primary driver. These findings reveal that autoantibodies can initiate feed-forward mechanisms that propagate systemic autoimmunity, independent of B cell-intrinsic antigen presentation. Competing Interest Statement The authors have declared no competing interest. Funder Information Declared National Institute of Arthritis and Musculoskeletal and Skin Diseases , R01AR073938 , R01AR075813 Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license . Back to top Previous Next Posted September 01, 2026. Download PDF Email Thank you for your interest in spreading the word about bioRxiv. NOTE: Your email address is requested solely to identify you as the sender of this article. Your Email * Your Name * Send To * Enter multiple addresses on separate lines or separate them with commas. You are going to email the following Antibody-dependent priming of spontaneous germinal centers by autoreactive B cells Message Subject (Your Name) has forwarded a page to you from bioRxiv Message Body (Your Name) thought you would like to see this page from the bioRxiv website. Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions. Share Antibody-dependent priming of spontaneous germinal centers by autoreactive B cells Danny Kim , Kristy Chiang , Andrea D Largent , Ragan A Pitner , Sivasankaran Munusamy Ponnan , Brock J McKinney , Richard G James , David J Rawlings , Shaun W Jackson bioRxiv 2026.08.27.745373; doi: https://doi.org/10.64898/2026.08.27.745373 Share This Article: Copy Citation Tools Antibody-dependent priming of spontaneous germinal centers by autoreactive B cells Danny Kim , Kristy Chiang , Andrea D Largent , Ragan A Pitner , Sivasankaran Munusamy Ponnan , Brock J McKinney , Richard G James , David J Rawlings , Shaun W Jackson bioRxiv 2026.08.27.745373; doi: https://doi.org/10.64898/2026.08.27.745373 Citation Manager Formats BibTeX Bookends EasyBib EndNote (tagged) EndNote 8 (xml) Medlars Mendeley Papers RefWorks Tagged Ref Manager RIS Zotero Tweet Widget Facebook Like Google Plus One Subject Areas All Articles Animal Behavior and Cognition (7952) Biochemistry (18592) Bioengineering (14731) Bioinformatics (44026) Biophysics (22416) Cancer Biology (19535) Cell Biology (26690) Clinical Trials (138) Developmental Biology (13869) Ecology (20821) Epidemiology (2067) Evolutionary Biology (25265) Genetics (16081) Genomics (23360) Immunology (18547) Microbiology (42139) Molecular Biology (17907) Neuroscience (92672) Paleontology (693) Pathology (2963) Pharmacology and Toxicology (5053) Physiology (8034) Plant Biology (15864) Scientific Communication and Education (2090) Synthetic Biology (4529) Systems Biology (10164) Zoology (2369)
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