Article Text

PDF
AB0102 Impairment of granzyme b-producing regulatory b cells exacerbated rheumatoid arthritis
  1. L Xu,
  2. F Hu,
  3. X Liu,
  4. L Zhu,
  5. L Ren,
  6. H Liu,
  7. H Zhu,
  8. Y Su
  1. Department of Rheumatology and Immunology, Peking University People's Hospital, Beijing, China

Abstract

Background Rheumatoid arthritis (RA) is a common and complex autoimmune disease characterized by chronic inflammation and cartilage/bone damage involving numerous cells, such as T cells, B cells, chondrocytes, fibroblasts [1]. B cells had long been well-demonstrated to participant in the development of RA [2]. Except producing specific antibody and inducing T cell activation, impaired immunosuppressive function of B cells further emphasized their roles in RA recently [3].

Objectives To investigate whether B cells could produce granzyme B and the potential role in the pathogenesis of Rheumatoid arthritis (RA).

Methods To reveal the expression of granzyme B in B cells, flow cytometry, PCR and Elispot were performed. The role of IL-21 and anti-BCR stimulation on granzyme B expression was assessed by in vitro stimulation assay. CD4+ T cell-B cell co-culture in the presence of granzyme B neutralizing antibody was performed to demonstrate the function of these cells. Then the levels of granzyme B in B cells between RA patients, OA patients as well as HCs were compared. Next,the correlation analysis between granzyme B-producing B cells and clinical features in RA patients was performed. Finally, the frequencies of granzyme B-producing B cells in RA patients before and after therapy were also evaluated using flow cytometry.

Results B cells could spontaneously produce granzyme B, which could be perpetuated by IL-21 and anti-BCR stimulation. The frequencies of Th1 and Th17 cells were significantly elevated under the condition of granzyme B blockade when granzyme B was neutralized in CD4+ T cell-B cell co-culture. In RA patients, but not OA patients and HCs, the frequencies of granzyme-B producing Bregs decreased significantly, which was functionally impaired and negatively correlated with disease activity score 28. Moreover, after effective clinical therapy, the frequencies could recover to nomal levels.

Conclusions B cells could exert the regulatory functions via granzyme B production. Under RA circumstance, these granzyme B-producing Bregs were impaired and contributed to the disease progression.

References

  1. Smolen JS, Aletaha D, McInnes IB, Rheumatoid arthritis, Lancet. 2016 Oct 22;388(10055):2023–2038. doi: 10.1016/S0140–6736(16)30173–8.

  2. Nakken B, Munthe LA, Konttinen YT, et al,B-cells and their targeting in rheumatoid arthritis–current concepts and future perspectives. Autoimmun Rev. 2011 Nov;11(1):28–34. doi: 10.1016/j.autrev.2011.06.010.

  3. Daien CI, Gailhac S, Mura T, Regulatory B10 cells are decreased in patients with rheumatoid arthritis and are inversely correlated with disease activity. Arthritis Rheumatol. 2014 Aug;66(8):2037–46. doi: 10.1002/art.38666.

References

Acknowledgements This study was supported by grants from the Natural Science Foundation of China (81671609, 81671604,31470039).

Disclosure of Interest None declared

Statistics from Altmetric.com

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.