We have shown that human transitional B cells are polarized towards regulatory cytokine expression and suppress pro-inflammatory Th1 response by autologous T cells. These cells were also shown to be increased in operationally tolerant renal transplant patients. Distinct subsets of transitional B cells (T1, T2) have previously been described. Here in we characterize the subsets of transitional b cells not only by the surface expression of various phenotypic markers but also by their ability to express either IL-10 or TNF-a when stimulated by CPG and CD40L. We then studied these cells in renal transplant recipients with stable graft function and those with graft dysfunction secondary to either non-immunological causes or rejection. We have also analysed these cells in a longitudinal study of an independent set of 20 renal transplant recipients who received depletional induction with alemtuzumab.
T1 transitional B cells constituted 23% of the transitional population and are characterized by CD24+++ CD38+++IgMhi IgDhi CD5hi CD10hi CD20hi CD40hi CD86hi CD1dhi phenotype. More importantly, T1 cells are distinguished from T2 based on a significantly lower co-expression of TNF-a, even when analysed on a pre-cell basis (p<0.01). Both subsets expressed IL-10 at similar frequencies. Patients with chronic antibody mediated rejection demonstrated a significantly lower ratio of T1/T2 cells suggesting a relative depletion of T1 in this patient group when compared to those with stable function (p<0.01). In renal transplant patients who received induction with alemtuzumab, transitional B cells constituted a significantly higher proportion of the reconstituted B cells early on (>50%). Interestingly in 3 patients who experienced an early acute rejection, the T1 transitional B cells are significantly depleted when compared to those with no evidence of rejection (p<0.05). In conclusion, we demonstrate a distinct subset of transitional B cells (T1) characterized by a relative inability to express pro-inflammatory cytokines. These cells are selectively depleted in the setting of both acute and chronic transplant rejection and this may in part explain the phenotypic and functional alterations within the transitional b cells in inflammatory clinical conditions. The specific role of these cells in the maintenance of allograft function needs a prospective study.
To cite this abstract in AMA style:Cherukuri A, Salama A, Carter C, Clark B, Rothstein D, Baker R. Characterization of Novel Human Transitional B Cell Subsets and Their Significance in Renal Transplantation [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/characterization-of-novel-human-transitional-b-cell-subsets-and-their-significance-in-renal-transplantation/. Accessed November 29, 2020.
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