Alemtuzumab induction combined with belatacept and rapamycin (ABR) maintenance immunotherapy effectively prevents costimulation blockade resistant rejection (CoBRR). We longitudinally investigated kinetics of repopulating B cell subsets and donor-specific allo-reactive antibody (DSA) in patients undergoing a novel calcineurin inhibitor-free ABR regimen within 36-month post-transplantation. 40 patients received a kidney allograft from either living (n=30) and deceased (n=10) donors. All patients were DSA free at transplant. Absolute peripheral blood B cell counts were analyzed by TruCount analysis, and the CD27-IgD and Bm1-Bm5 (IgD/CD38) classifications were utilized to define the B cell differentiation. Serum samples were screened for DSA by a microparticle-based FACS analysis, and the specificities of DSA to HLA class I and II was determined by a Luminex-based assay. Profound B cell depletion post-alemtuzumab induction was followed by rapid repopulation. The reconstituting B cells were predominantly naïve B cells (CD27^–IgG⁺, Bm1/Bm2 subsets) after 6 months post-transplantation. In contrast, the frequency of memory B cell subsets including switched (CD27⁺IgD^–), un-switched (CD27⁺IgD⁺), and exhausted (CD27^–IgD^–) memory cells, and early (Bm5-early)/later (Bm5-late) memory B cells was significantly lower than baseline levels between 6 and 36 months post-depletional induction (p=0.0001). Additionally, regulatory B cells defined as CD38^hiCD24^hiIgM^hiCD20^hi subset was significantly higher than baseline 6 months post-transplantation (p=0.0001). DSA was not detectable in 35 patients with 36 months post-transplantation. No patients developed ABMR, though 5 patients developed DSA: 2 class II (DQ), 2 class I, and one associated with multiple failed pregnancies (class I and class II). The repopulating B cells in patients undergoing novel ABR immunosuppression demonstrate increased naïve and regulatory B populations, and the reconstitution of memory B cells is significantly inhibited without detectable allo-reactive antibody in most patients after transplantation. These findings suggest that lymphocyte depletion and belatacept-based maintenance regimen achieves anti-rejection effects by promoting naïve and regulatory B cells while suppressing memory B cells after transplantation. This regimen warrants formal, prospective, comparative study.

CITATION INFORMATION: Gao Q., Mehta A., Guasch A., Ghali A., Kirk A., Xu H. B Cell Reconstitution: 36-Month Analysis of Patients Post-Alemtuzumab Induction Followed by Belatacept-Based Immunosuppression Am J Transplant. 2017;17 (suppl 3).

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