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

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)CD3(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.