Transcriptomic Signature of the CD24hiCD38hi Transitional B Cells Associated With an Immunoregulatory Phenotype in Renal Transplant Recipients

• Published in: American journal of transplantation Vol. 16; no. 12; pp. 3430 - 3442
• Main Authors: Bigot, J., Pilon, C., Matignon, M., Grondin, C., Leibler, C., Aissat, A., Pirenne, F., Cohen, J. L., Grimbert, P.
• Format: Journal Article
• Language: English
• Published: Malden Elsevier Limited 01.12.2016
• Subjects: Antibodies; B cell biology; biomarker; CD19 antigen; CD38 antigen; CD9 antigen; fusion proteins and monoclonal antibodies: costimulation molecule specific; Gene expression; Graft rejection; Health risk assessment; immunobiology; Immunological tolerance; Immunoregulation; immunosuppressant; Interleukin 10; Kidney transplantation; kidney transplantation/nephrology; Lymphocyte receptors; Lymphocytes B; Lymphocytes T; Population studies; T cell receptors; translational research/science
• ISSN: 1600-6135; 1600-6143
• DOI: 10.1111/ajt.13904

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+CD38hiCD24hi 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 CD24hiCD38hi, (ii) CD24+CD38−, and (iii) CD24intCD38int B cells. Transcriptome bioinformatic analysis revealed a particular signature for the CD24hiCD38hi population. Phenotypic analysis showed that CD24hiCD38hi 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 CD24hiCD38hi 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 CD24hiCD38hi 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. This study highlights a specific transcriptomic and phenotypic signature of human transitional CD24hiCD38hi B cells associated with immunoregulatory properties.