A stromal platform for robust expansion of functional IL-10–producing B cells for immune regulation

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Abstract

IL-10–producing B cells exert immunosuppressive effects, yet their low abundance and poor in vitro viability have limited their therapeutic application. Here, we developed a stromal coculture system using MS5 cells engineered to express human CD40L, BAFF, and IFN-β1 (MS5-3F, for “3 factors”), which enables robust induction and greater than 1000-fold expansion of human IL-10–producing B cells. The expanded cells showed phenotypic and transcriptional profiles characteristic of unswitched (IgM+) plasmablasts and potently suppressed CD4+ T cell proliferation in an IL-10–dependent manner. MS5-3F–expanded B cells also increased the frequency of regulatory T cells in vitro, an effect that was not abrogated by IL-10/IL-10R blockade, suggesting contributions from additional mechanisms. IL-10 production originated predominantly from naive B cells, rather than memory B cells. Furthermore, B cells from patients with systemic lupus erythematosus, despite impaired IL-10 production under conventional conditions, were efficiently differentiated into IL-10–producing B cells using this system. The expanded cells showed minimal IgG-secreting output. Our platform offers a scalable strategy for generating human regulatory B cells, laying the foundation for B cell–based immunotherapies.

Authors

Ryo Kawakami, Keisuke Imabayashi, Akemi Baba, Yuichi Saito, Kazuhiko Kawata, Yutaro Yada, Airi Shibata, Rinka Ito, Ryo Kurasawa, Ryota Higuchi, Sungyeon Park, Hiroaki Niiro, Shinya Tanaka, Yoshihiro Baba