Anti-CD45RB antibody therapy attenuates renal ischemia-reperfusion injury by inducing regulatory B cells

Background 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. Methods Usingmouse models, including T cell-deficient (RAG1 knockout and TCRa knockout)mice and B cell-deficient (mMT)mice, we investigated the effects of regulatory B cells and anti-CD45RB on IRI and the mechanisms underlying these effects. Results 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 inwild-typemicewith B cell depletion. Furthermore, B cell-deficientmice receiving B cells fromIL-10 knockout mice (but not from wild-type mice) did not show renal protection against IRI when treated with anti-CD45RB. Conclusions 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.