Transcriptomic Signature of the CD24hi CD38hi Transitional B Cells Associated With an Immunoregulatory Phenotype in Renal Transplant Recipients

Abstract

The role of B cells after transplant regarding allograft rejection or tolerance has become a topic of major interest. Recently, in renal transplant recipients, a B cell signature characterized by the overexpression of CD19⁺ CD38^hi CD24^hi transitional B cells has been observed in operationally tolerant patients and in belatacept-treated patients with significantly lower incidence of donor-specific antibodies. The phenotypic and functional characterization of these transitional B cells is far from exhaustive. We present the first transcriptomic and phenotypic analysis associated with this cell phenotype. Three populations were studied and compared: (i) transitional CD24^hi CD38^hi , (ii) CD24⁺ CD38^- , and (iii) CD24^int CD38^int B cells. Transcriptome bioinformatic analysis revealed a particular signature for the CD24^hi CD38^hi population. Phenotypic analysis showed that CD24^hi CD38^hi transitional B cells also expressed CD9, CD10, CD1b and inducible T cell costimulator ligand (ICOS-L) markers. In addition, we found enrichment of IL-10⁺ cells among CD24^hi CD38^hi cells expressing ICOS-L and CD1b, the latter showing regulatory properties. Renal transplant recipients treated with belatacept exhibited significant expression of CD1b. Our results show that transitional CD24^hi CD38^hi B cells exhibit a distinct and specific profile, and this could be helpful for understanding of immune-regulatory mechanisms and immune monitoring in the field of organ transplant and autoimmune disease.

Keywords: B cell biology; biomarker; fusion proteins and monoclonal antibodies: costimulation molecule specific; immunobiology; immunosuppressant; kidney transplantation/nephrology; translational research/science.