Dynamic features of B lymphocyte reconstruction in peripheral blood of patients with immune tolerance induced with combined transplantation of kidney and bone marrow / 吉林大学学报(医学版)

ABSTRACT

Objective:To study the dynamic characteristics of reconstruction of B lymphocytes in peripheral blood at different time points in the patients with immune tolerance induced by combined transplantation of kidney and bone marrow,and to provide the basis for the further illumination of the role of B lymphocytes in immune tolerance of organ transplantation.Methods:Five patients(Pt.A,Pt.B,Pt.C,Pt.D,and Pt.E)with end stage of kidney disease received kidney and bone marrow transplantation after induction therapy.Immunosuppression was discontinued gradually.The number of B lymphocytes and the distribution of subsets of B lymphocytes in peripheral blood were detected by flow cytometry in the patients before and after transplantation,and the dynamic changes of B lymphocytes at different time points were compared.The distribution of immunoglobulin heavy chain variable region(IGHV)was analyzed using next generation sequencing technology.Results:Four patients were enrolled in the study expect one patient with graft failure(Pt.C).The B lymphocyte counts of Pt.A,Pt.B and Pt.D recovered approximately 1 year after transplantation and Pt.E experienced delayed reconstitution.The B lymphocyte recovery was accompanied by a high frequency of CD20+CD24highCD38hightransitional B lymphocytes and a diversified clonal repertoire.All patients showed the prevalence of CD20+CD27+ memory B cells around 6 months after transplantation.Through the calculation of Shannon diversity index(SDI)of IGHV at each time point after transplantation,the SDI of IGHV for all transplant recipients at 182 d after transplantation was significantly lower than before transplantation(P=0.004),and this index was gradually recovered at approximately 1 year after transplantation.The calculation of somatic mutation of B lymphocyte IGHV gene sequence at different time points showed that the somatic mutation rate was elevated at 182 d for all patients except Pt.B(P = 0.032). Conclusion:The presence of mutated memory B lymphocytes in peripheral blood of the patients with kidney and bone marrow transplantation is found,and the B lymphocytes play the potential contribution to tolerance induction.