Distinct synovial fluid B-cell differentiation and activation profiles in rheumatoid arthritis

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.

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BibTeX RIS

BibTeX

@misc{huang2026distinct,
  title = {{Distinct synovial fluid B-cell differentiation and activation profiles in rheumatoid arthritis}},
  author = {W. Huang and S. Ghannoum and K. Wangriatisak and A. Hooijsma and M. Nakazawa and L. Franzen and S. Petkov and K. Chatzidionysiou and V. Malmström and C. Grönwall},
  howpublished = {bioRxiv},
  year = {2026},
  month = sep,
  doi = {10.64898/2026.09.24.754012},
  url = {https://www.biorxiv.org/content/10.64898/2026.09.24.754012v1},
  note = {CC BY-NC},
}

RIS

TY  - UNPB
TI  - Distinct synovial fluid B-cell differentiation and activation profiles in rheumatoid arthritis
AU  - W. Huang
AU  - S. Ghannoum
AU  - K. Wangriatisak
AU  - A. Hooijsma
AU  - M. Nakazawa
AU  - L. Franzen
AU  - S. Petkov
AU  - K. Chatzidionysiou
AU  - V. Malmström
AU  - C. Grönwall
PY  - 2026
DA  - 2026/09/24
PB  - bioRxiv
DO  - 10.64898/2026.09.24.754012
UR  - https://www.biorxiv.org/content/10.64898/2026.09.24.754012v1
AB  - 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.
ER  -

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