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P032 Capture of IGA immune complexes and enrichment in IGA IG gene expression suggest a role for synovial FCRL4+ B cells in the link between mucosal and joint inflammation
  1. J Cameron1,
  2. E Clay1,
  3. K Amara2,
  4. G Vidal Pedrola3,
  5. N Sippl2,
  6. A Filer1,
  7. K Raza1,
  8. V Malmstrom2,
  9. D Scheel-Toellner1
  1. 1Rheumatology Research Group, University of Birmingham, Birmingham, UK
  2. 2Rheumatology Unit, Karolinska University Hospital, Karolinska Institutet, Solna, Sweden
  3. 3Musculoskeletal Research Group, Faculty of Medical Sciences, Newcastle University, Newcastle, UK


Introduction Increasing evidence points to the autoimmune process of rheumatoid arthritis (RA) originating at mucosal surfaces. Previous work from our group described a subset of B cells in the synovium and synovial fluid (SF) of RA patients distinguishable by their expression of Fc-like receptor 4 (FcRL4) and elevated expression of RANKL, indicating a unique pathogenic function.1,2 B cells expressing FcRL4 were originally described as a distinct memory B cell subset in human tonsils where they are localised in the epithelium.3 We have recently shown in RA that they are enriched in clones recognising citrullinated autoantigens.3 Recent in vitro work suggested that FcRL4 is a low affinity receptor for aggregated IgA.4


  • Investigate the interactions between IgA and FcRL4 and FcRL4+ B cells using tonsil and SF B cells, and transfected cell lines.

  • Examine the distribution of Ig classes by flow cytometry and PCR.

Methods Mononuclear cells were isolated from SF (n=10) and tonsil, labelled for CD19, FcRL4, IgA, and IgG and analysed by flow cytometry. In experiments identifying BCRs and relative loads of surface bound IgA; SFMCs were washed in an acidic buffer to remove receptor-bound proteins before staining. Heat-aggregated purified human IgA was added to assess IgA binding to FcRL4 +B cells. Single B cells were sorted from SF of RA patients and their constant region genes probed for identification of their Ig subclass by PCR.

Results We show that ex vivo SF FcRL4+ B cells have a significantly higher load of IgA bound to their surface (p=0.0001) than FcRL4- B cells. Following in vitro removal of surface bound IgA, FcRL4 +B cells bind heat-aggregated IgA (p=0.03 vs control). We also demonstrate that a significantly higher proportion of FcRL4+ B cells use IgA BCRs (p=0.0061) by flow cytometry, and by probing constant region genes by PCR an enrichment for Ig genes for coding the IgA1 isotype (p=0.009) was found. Furthermore, three out of eight of the antibodies recognising citrullinated peptides had been cloned from FcRL4+ IgA+ B cells.

Conclusions In conclusion, their specificity for citrullinated antigens, ability to capture IgA immune complexes through via FcRL4 and enrichment in IgA1 subclass expression, suggest a role for FcRL4 +B cells in the mucosal origin of joint inflammation.


  1. . Yeo L, et al. Ann Rheum Dis2011;70:2022–2028. doi:10.1136/ard.2011.153312

  2. . Yeo L, et al. Ann Rheum Dis2015;74:928–935. doi:10.1136/annrheumdis-2013-204116

  3. . Amara K, et al. J. Autoimmun2017. doi:10.1016/j.jaut.2017.03.004

  4. . Wilson TJ, et al. J Immunol2012;188;4741–4745. doi:10.4049/jimmunol.1102651

Acknowledgements This work was supported by the Medical Research Council UK, Rheumatoid Arthritis Pathogenesis Centre of Excellence, and Karolinska Institutet Foundations for Rheumatology Research.

Disclosure of interest None declared

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