Session Information
Date: Saturday, November 16, 2024
Title: Abstracts: B Cell Biology & Targets in Autoimmune & Inflammatory Disease I
Session Type: Abstract Session
Session Time: 1:00PM-2:30PM
Background/Purpose: Sjögren’s syndrome (SjS) is a chronic inflammatory disorder, characterized by formation of autoantibodies. Over time rheumatoid factor (RF) clones can give rise to cryoglobulinemic vasculitis and extranodal marginal zone lymphoma. The latter typically presents in the salivary glands. It is generally speculated that this results from ectopic proliferation of RF clones in the salivary glands.
Methods: We performed 18F-fluorolevothymidine PET-scans to identify proliferating cells in affected salivary glands and reactive cervical lymph nodes in patients with severe SjS. All included patients (n=16) satisfied the ACR classification criteria. Ultrasound guided biopsies were performed based on PET-avidity. To comparatively characterize SjS autoreactive B cell responses we combined mass-spectrometry antibody sequencing of RF, anti-Ro60, anti-Ro52 and anti-La with multi-omic single-cell analysis (RNAseq, BCRseq, CITEseq) of sorted B cells.
Results: Reactive cervical lymph nodes were enriched for FCRL5+ and interferon-response gene expressing B cells. RF clones proliferated as large IgM+ ZEB+ atypical memory B cell clones in lymph node follicles. There they co-expressed FCRL5, FGR and HCK, enhancers of B cell receptor-mediated activation to immune complexes. SjS LN FCRL5+ memory B cells were transcriptionally similar to a FCRL5+ population in tonsils of patients with chronic tonsilitis. In inflamed salivary glands, RF B cells infiltrated as very large, highly intra-clonally diversified memory B cell clones and clonally related plasma cells. There, only a small fraction of RF clones proliferated at a low level, expressing markers of dysfunction.
Anti-Ro60, anti-Ro52 and anti-La clones proliferated as small IgG1+ CXCR5- memory B cells clones in lymph nodes. In salivary glands, these clones did not proliferate. Instead, they infiltrated as a large number of small plasma cell clones that co-localized with ductal epithelial cells.
After follow-up a number of patients developed clinically overt cryoglobulinemic vasculitis and lymphoma. Rheumatoid factor clones were identified in cryoglobulins that dominated in previous biopsies.
Conclusion: RF clones predominantly proliferate in reactive cervical lymph nodes compared to affected salivary glands of SjS patients. In lymph nodes RF occur as atypical FCLR5+ memory B cell clones, which give rise to highly intra-clonally diversified memory B cell clones that dominate affected salivary glands. These precede cryoglobulinemic vasculitis and lymphomagenesis.
To cite this abstract in AMA style:
Papadimitriou T, Wang J, He X, van der Zade S, Krekorian M, Singh P, Dik E, Pruijn G, Gordon T, Koenen H, Huijnen M, Thurlings R. Rheumatoid Factor B Cell Clones Proliferate Predominantly as Atypical Memory B Cells in Reactive Cervical Lymph Node Follicles Compared to Extrafollicular Sites in Affected Salivary Glands of SjS Patients [abstract]. Arthritis Rheumatol. 2024; 76 (suppl 9). https://acrabstracts.org/abstract/rheumatoid-factor-b-cell-clones-proliferate-predominantly-as-atypical-memory-b-cells-in-reactive-cervical-lymph-node-follicles-compared-to-extrafollicular-sites-in-affected-salivary-glands-of-sjs-pati/. Accessed .« Back to ACR Convergence 2024
ACR Meeting Abstracts - https://acrabstracts.org/abstract/rheumatoid-factor-b-cell-clones-proliferate-predominantly-as-atypical-memory-b-cells-in-reactive-cervical-lymph-node-follicles-compared-to-extrafollicular-sites-in-affected-salivary-glands-of-sjs-pati/