Background/Purpose: Impaired function of regulatory B10 cells has been shown in autoimmune diseases. However, the underlying mechanism is still obscure. In the present study, we investigated the potential contribution of CD70-CD27 interaction to B10 cell impairment in rheumatoid arthritis.

Methods: A total of 120 RA patients and 73 healthy controls were enrolled in our study. CD19⁺CD24^hiCD27⁺ regulatory B10 cells and CD19⁺IL-10⁺ B cells in PBMCs were assessed by flow cytometry. CD70, CD27, IL-10, TNF-α, IL-1β, IL-6, IFN-γ and IL-17 was evaluated by qPCR. PBMCs from healthy controls were pretreated with or without anti-CD70 antibody before anti-CD3 plus anti-CD28 antibodies treatment. Soluble CD27 and IL-10 in sera and supernatants was detected by ELISA. CD70 expression on CD4⁺ T and CD19⁺ B cells were assessed by flow cytometry in RA and healthy controls.

Results: The frequencies of CD19⁺CD24^hiCD27⁺ regulatory B10 cells were decreased and thier IL-10-producing competency was impaired in patients with RA. The impairment of CD19+CD24hiCD27+ B10 cells was partially attributed to the decreased expression of CD27 induced by upregulated CD70 on CD19+ B cells and CD4+ T cells. The frequencies of CD19⁺CD24^hiCD27⁺ regulatory B10 cells could be restored after blocking CD70-CD27 interaction by anti-CD70 antibody. Furthermore, CD70-CD27 interaction significantly elevated the IL-10 expression accompanied and compensated for the number decreasing of CD19⁺CD24^hiCD27⁺ B cells.

Conclusion: CD70-CD27 interaction may play a critical role in the numerical and functional impairment of regulatory B10 cells, thus contributing to RA pathogenesis.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/cd70-mediated-cd27-downregulation-contributed-to-regulatory-b10-cell-impairment-in-rheumatoid-arthritis/