---
title: "Distinct synovial fluid B-cell activation and differentiation profiles in rheumatoid arthritis"
id: "biorxiv-2-distinct-synovial-fluid-b-cell-differentiation-and-activation-profiles-in"
canonical_url: "https://medichelpline.com/clinical-feed/biorxiv-2-distinct-synovial-fluid-b-cell-differentiation-and-activation-profiles-in"
content_type: "clinical_feed_article"
specialty: "General"
source_name: "bioRxiv (Biomedical Preprints)"
source_url: "https://www.biorxiv.org/content/10.64898/2026.09.24.754012v1?rss=1"
published_at: "2026-09-29T12:00:00.000Z"
evidence_level: "Verified Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Distinct synovial fluid B-cell activation and differentiation profiles in rheumatoid arthritis
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/biorxiv-2-distinct-synovial-fluid-b-cell-differentiation-and-activation-profiles-in
- **Specialty:** [General](https://medichelpline.com/clinical-feed/general.md)
- **Primary Source:** bioRxiv (Biomedical Preprints)
- **Source URL:** [Original Journal Publication](https://www.biorxiv.org/content/10.64898/2026.09.24.754012v1?rss=1)
- **Published At:** 2026-09-29T12:00:00.000Z
- **Evidence Rating:** Verified Feed
## Executive GIST (TL;DR)
- The study examined paired blood and synovial fluid from patients with **ACPA-positive rheumatoid arthritis (RA)** (N=12), seronegative RA (N=10) and spondyloarthritis (N=8) to profile B-cell states at sites of inflammation. - There was a pronounced enrichment of **CD11c+CD21- B cells** in synovial fluid across all disease groups, comprising on average 67% (ACPA+ RA), 49% (seronegative RA) and 51% (spondyloarthritis) of CD19+ cells. - In ACPA-positive RA specifically, authors observed higher proportions of **CD11c+IgG+CD27low** B cells and multiple stages of pre-plasmablasts, indicating increased extrafollicular plasmablast differentiation at the inflamed joint. - The **CD11c+CD21- population** displayed markers consistent with **BCR activation**, cellular proliferation, and antigen-presentation capability, defining an activated, antigen-experienced synovial B-cell profile. - A parallel T-cell program differed by serostatus: **LAG3+CTLA4+TIGIT+ peripheral helper T-cell** program was associated with ACPA-positive RA, whereas seronegative RA showed a **CCR6+ Th17-skewing** phenotype. - Single-cell spatial proteomics identified a unique surface architecture on **CD11chighCD21low** B cells, including a BCR co-receptor–tetraspanin signature with **CD72–CD81** co-localization that was elevated in RA. - Additional immune-modules in CD11c+ cells included **CD44–CD52/CD59** and **MHCII–CD40/CD84** modules not seen in other B-cell subsets, implying complement resistance and enhanced antigen presentation. - Overall, CD11c+CD21- B cells are heterogeneous across disease states; while an activated antigen-experienced synovial profile was common, **ACPA+ RA** displayed distinctive evidence of increased extrafollicular plasmablast differentiation and receptor organization favoring BCR responsiveness. - Funding sources and competing interests were reported: supported by Swedish Rheumatism Association, Swedish Research Council and foundations; two authors employed by Pixelgen Technologies AB were disclosed.
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Wenqi Huang 1 Karolinska Institutet; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Wenqi%2BHuang%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Huang%20W&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AWenqi%2BHuang%2B) Salim Ghannoum 1 Karolinska Institutet; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Salim%2BGhannoum%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Ghannoum%20S&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3ASalim%2BGhannoum%2B) Kittikorn Wangriatisak 1 Karolinska Institutet; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Kittikorn%2BWangriatisak%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Wangriatisak%20K&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AKittikorn%2BWangriatisak%2B) Annelien Hooijsma 1 Karolinska Institutet; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Annelien%2BHooijsma%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Hooijsma%20A&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AAnnelien%2BHooijsma%2B) Maho Nakazawa 1 Karolinska Institutet; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Maho%2BNakazawa%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Nakazawa%20M&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AMaho%2BNakazawa%2B) Lovisa Franzén 2 Pixelgen Technologies AB * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Lovisa%2BFranz%C3%A9n%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Franz%C3%A9n%20L&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3ALovisa%2BFranz%25C3%25A9n%2B) Stefan Petkov 2 Pixelgen Technologies AB * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Stefan%2BPetkov%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Petkov%20S&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AStefan%2BPetkov%2B) Katerina Chatzidionysiou 1 Karolinska Institutet; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Katerina%2BChatzidionysiou%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Chatzidionysiou%20K&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AKaterina%2BChatzidionysiou%2B) Vivianne Malmström 1 Karolinska Institutet; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Vivianne%2BMalmstr%C3%B6m%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Malmstr%C3%B6m%20V&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AVivianne%2BMalmstr%25C3%25B6m%2B) Caroline Grönwall 1 Karolinska Institutet; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Caroline%2BGr%C3%B6nwall%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Gr%C3%B6nwall%20C&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3ACaroline%2BGr%25C3%25B6nwall%2B) * [ORCID record for Caroline Grönwall](http://orcid.org/0000-0002-9111-5537 "Open in new tab") * For correspondence: caroline.gronwall@ki.se * [Abstract](https://www.biorxiv.org/content/10.64898/2026.09.24.754012v1)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_art/node:5824189/1) * [Info/History](https://www.biorxiv.org/content/10.64898/2026.09.24.754012v1.article-info)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_info/node:5824189/1) * [Metrics](https://www.biorxiv.org/content/10.64898/2026.09.24.754012v1.article-metrics)[](https://www.biorxiv.org/panels_ajax_tab/article_tab_metrics/node:5824189/1) * [Supplementary material](https://www.biorxiv.org/content/10.64898/2026.09.24.754012v1.supplementary-material)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_data/node:5824189/1) * [ Preview PDF](https://www.biorxiv.org/content/10.64898/2026.09.24.754012v1.full.pdf+html)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_pdf/node:5824189/1) ![Loading](https://www.biorxiv.org/sites/all/modules/contrib/panels_ajax_tab/images/loading.gif) ## Abstract CD11c+CD21- B cells are overrepresented in rheumatoid arthritis (RA). Here we delineate their functional state at site of inflammation and its molecular basis. Phenotypic profiling of paired blood and synovial fluid from patients with anti-citrullinated protein antibody (ACPA) seropositive RA (N=12), seronegative RA (N=10) and spondyloarthritis (N=8), demonstrated a striking enrichment of CD11c+CD21- B cells in synovial fluid in all three diseases (average of CD19+ cells: 67%, 49% and 51%). In ACPA-positive RA we identified increased proportions of CD11c+IgG+CD27low cells and several stages of pre-plasmablasts. The CD11c+CD21- cells had a phenotype indicating BCR activation, proliferation, and antigen presentation. This B-cell profile was mirrored by a LAG3+CTLA4+TIGIT+ peripheral helper T-cell program in ACPA-positive RA, contrasting a CCR6+ Th17-skewing in seronegative RA. Single-cell spatial proteomics revealed a unique CD11chighCD21 low B-cell surface architecture including a BCR co-receptor-tetraspanin signature with CD72-CD81 co-localization, which was elevated in RA. CD11c+ cells also displayed CD44-CD52/CD59 and MHCII-CD40/CD84 immune-modules absent in other B-cell subsets. In summary, CD11c+CD21- B cells are highly diverse, and while an activated antigen-experienced synovial profile was shared between disease groups, ACPA+ RA showed evidence of increased extrafollicular plasmablast differentiation. Surface receptor organization implicated a favoured BCR responsiveness, complement resistance and antigen presentation. ### Competing Interest Statement Lovisa Franzen and Stefan Petkov are employed by Pixelgen Technologies AB ## Funder Information Declared Swedish Rheumatism Association, R-1012541 Swedish Research Council, 2023-02497, R-1033940 King Gustaf V’s 80-year Foundation, FAI-2023-0956, FAI-2025-1172 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 4.0 International license](http://creativecommons.org/licenses/by-nc/4.0/). bioRxiv and medRxiv thank the following for their generous financial support: > The Chan Zuckerberg Initiative, Cold Spring Harbor Laboratory, the Sergey Brin Family Foundation, California Institute of Technology, Centre National de la Recherche Scientifique, Fred Hutchinson Cancer Center, Imperial College London, Massachusetts Institute of Technology, Stanford University, The University of Edinburgh, University of Washington, and Vrije Universiteit Amsterdam. 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[ Download PDF](https://www.biorxiv.org/content/10.64898/2026.09.24.754012v1.full.pdf) Print/Save Options [Download PDF](https://www.biorxiv.org/content/biorxiv/early/2026/09/29/2026.09.24.754012.full.pdf)Full Text & In-line FiguresXML [More Info](https://www.biorxiv.org/about/FAQ#PrintOptions "More Information on Print/Save Options") [Supplementary Material ](https://www.biorxiv.org/content/10.64898/2026.09.24.754012v1.supplementary-material) [ Email](https://www.biorxiv.org/ "Email this Article") [ Share](https://www.biorxiv.org/) Distinct synovial fluid B-cell differentiation and activation profiles in rheumatoid arthritis Wenqi Huang, Salim Ghannoum, Kittikorn Wangriatisak, Annelien Hooijsma, Maho Nakazawa, Lovisa Franzén, Stefan Petkov, Katerina Chatzidionysiou, Vivianne Malmström, Caroline Grönwall bioRxiv 2026.09.24.754012; doi: https://doi.org/10.64898/2026.09.24.754012 This article is a preprint and has not been certified by peer review [[what does this mean?](https://www.biorxiv.org/about/FAQ#unrefereed)]. 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