CD19⁺CD38^hiCD24^hi immature transitional B cells may represent a biomarker for transplantation tolerance in kidney transplant (KTx) recipients (Cherukuri A, et al. J Am Soc Nephrol. 2014 and Nouël A, et al. Kidney Int. 2014). A higher frequency of immature transitional B cells has been observed in KTx recipients who were either spontaneously operationally tolerant or had tolerance induced by a combined bone marrow and KTx protocol (Baron D, et al. Kidney Int. 2015). Tolerant KTx recipients displayed the same frequency of immature transitional B cells as healthy controls (Newell KA, et al. Am J Transplant. 2015). Recipients with a lower frequency of immature transitional B cells were more prone to acute rejection (Shabir S, et al. Am J Transplant. 2015). We have reported that facilitating cell-enriched hematopoietic stem cell allografts (FCRx) induce tolerance to renal allografts in HLA-mismatched living donor KTx recipients (Leventhal J, et al. Sci Transl Med. 2012 and Leventhal J, et al. Transplantation. 2015). To date there are 22 subjects completely off immunosuppression (IS) with stable renal function from 2 months to over 7 years. In the present study, we determined whether immature transitional B cells were present in tolerant KTx recipients treated with FCRx. Subjects with high levels of durable donor chimerism were weaned from IS over a year. Eighteen months after the transplantation, PBMCs from eleven chimeric tolerant KTx recipients off all IS were stained with a nine-color immunophenotyping panel. Tolerant KTx treated with FCRx exhibited a similar proportion of CD19⁺CD38^hiCD24^hi immature transitional B cells (around 3% of total CD19⁺ B cell population) compared to healthy controls. Moreover, the changes of immature transitional B cells remained stable over a period of one year in four tolerant recipients for whom serial samples were available (up to 36 months), suggesting that the changes of immature transitional B cells noted in our tolerant KTx recipients is maintained over time. In summary, our preliminary immunomonitoring data support a role for CD19⁺CD38^hiCD24^hi immature transitional B cells in tolerance seen in FCRx KTx recipients.

CITATION INFORMATION: Wen Y, Merchak A, Huang Y, Xu H, Kahn L, Leventhal J, Ildstad S. CD19⁺CD38^hiCD24^hi Immature Transitional B Cells in PBMCs of Tolerant Kidney Recipients of Facilitating Cell-Enriched Hematopoietic Stem Cells and Renal Allografts. Am J Transplant. 2017;17 (suppl 3).

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