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J Am Soc Nephrol. 2019 Oct;30(10):1870-1885. doi: 10.1681/ASN.2018101067. Epub 2019 Jul 11.

Anti-CD45RB Antibody Therapy Attenuates Renal Ischemia-Reperfusion Injury by Inducing Regulatory B Cells.

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Transplantation Research Institute and.
Department of Medicine, Graduate School, Seoul National University College of Medicine, Seoul, Republic of Korea.
Transplantation Center and.
Asan Institute for Life Sciences, Asan Medical Center, Seoul, Republic of Korea; and.
Department of Convergence Medicine, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Department of Medicine, Graduate School, Seoul National University College of Medicine, Seoul, Republic of Korea;
Department of Surgery, Seoul National University Hospital, Seoul, Republic of Korea.
Transplantation Research Institute and



Regulatory B cells are a newly discovered B cell subset that suppresses immune responses. Recent studies found that both anti-CD45RB and anti-Tim-1 treatments regulate immune responses by inducing regulatory B cells; however, the role of these cells in renal ischemia-reperfusion injury (IRI) is unknown.


Using mouse models, including T cell-deficient (RAG1 knockout and TCRα knockout) mice and B cell-deficient (μMT) mice, we investigated the effects of regulatory B cells and anti-CD45RB on IRI and the mechanisms underlying these effects.


Adoptive transfer of regulatory B cells before or after IRI attenuated renal IRI. Anti-CD45RB treatment with or without anti-Tim-1 before IRI increased renal infiltration of CD19+Tim-1+ regulatory B and regulatory T cells. Anti-CD45RB decreased serum creatinine levels, pathologic injury score, tubular apoptosis, and proinflammatory cytokines levels, whereas IL-10 levels increased. Following IRI, anti-CD45RB with or without anti-Tim-1 also induced regulatory B cells, improving renal function and tubular regeneration. In RAG1 knockout mice with B cell transfer, TCRα knockout mice, and wild-type mice with T cell depletion, anti-CD45RB increased regulatory B cells and attenuated IRI. However, anti-CD45RB did not attenuate IRI in RAG1 knockout mice with T cell transfer or μMT mice and induced only mild improvement in wild-type mice with B cell depletion. Furthermore, B cell-deficient mice receiving B cells from IL-10 knockout mice (but not from wild-type mice) did not show renal protection against IRI when treated with anti-CD45RB.


Anti-CD45RB treatment attenuated acute renal injury and facilitated renal recovery after IRI through induction of IL-10+ regulatory B cells, pointing to anti-CD45RB as a potential therapeutic strategy in renal IRI.


anti-CD45RB; anti-Tim-1; ischemia-reperfusion injury; regulatory b cell


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