Background/Purpose: Cytotoxic T lymphocyte antigen-4 (CTLA-4) competes with CD28 for binding the CD80/CD86 on antigen presenting cells to inhibit further activation of T cells. Abatacept, a CTLA-4 fusion protein, has been used for rheumatoid arthritis (RA) treatment worldwide. The aim of this study was to test whether CTLA-4 regulates human B cell functions.

Methods: The influence of abatacept on B cell functions in both in vitro and in vivo conditions was assayed. Blood was taken from 30 patients with RA before and after abatacept treatment. RA disease activity was measured using the Disease Activity Score 28 using ESR (DAS28-ESR). Serum level of rheumatoid factor (RF), anti-cyclic citrullinated peptide antibody (ACPA), and anti-tetanus toxoid antibodies was measured by ELISA. The expression of CD80/CD86 on B cells was detected using immunofluorescent staining. Purified human B cells from healthy donors were treated by T-independent (TI) and T-dependent (TD) stimulation in the presence of abatacept and cell proliferation, cytokine production, plasma cell differentiation, and antibody production were measured.

Results: RA patients showed significant clinical improvement after 6 months of abatacept treatment and a decrease in mean DAS28-ESR score was found. Abatacept transiently reduced the level of CD80/CD86 on peripheral blood memory B cells. A decrease in serum RF level was observed in our RA patients during the 6 months of abatacept treatment. However, the serum level of ACPA and anti-tetanus toxoid antibodies were not influenced. In the in vitro assays, we observed that the CD80 and CD86 induced by T-independent (TI) but not T-dependent (TD) stimulation was significantly downregulated by abatacept at both the mRNA level and protein level. TI-induced TNF-α and IL-6 production by B cells was also reduced by abatacept. Neither TI nor TD- stimulated B cell proliferation was reduced by abatacept in ³H-thymidine incorporation assay. Finally, abatacept inhibited Daudi-B cell induced allogeneic T cell proliferation, indicating a significant blockade of T-B interaction by abatacept.

Conclusion: Abatacept may decrease RF level by blocking the interaction of CD28 with CD80/CD86, therefore preventing B cells from T cells’ help for differentiation into plasma cells. Our results also demonstrate that abatacept may provoke a negative reverse signal to B cells to further regulate B cells activation.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-influence-of-abatacept-on-human-b-cell-functions/