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Aim To monitor B cell subsets in peripheral circulation to find a distinctive phenotypic signature of rejection in our cohort. Methods The study population consisted of 211 consecutive first renal allograft recipients who were followed up for 12 months post-transplant. One ml of EDTA peripheral venous blood was collected pre- transplant, 1 month, 3 months, 6 months, 12 months post-transplant and at the time of graft rejection. A multicolour flowcytometry was performed to monitor the percentage of peripheral Plasma cells (CD20-CD38+CD138+), Total B-cells (CD20+), Naïve B-cells (CD20+CD27-CD38-), Activated B-cells (CD20+CD38+CD138-) and Memory B-cells (CD20+CD138-CD27+). Results Of 211 cases of first kidney allograft recipients, 35 (16.58%) recipients had 38 episodes of acute allograft rejection. Percentage of activated B cells and Memory B-cells were found to be significantly higher in uremic patients ( n = 78) than those of healthy persons ( n = 40) (20.81 ± 0.7616 % vs. 14.37 ± 0.5972%, p < 0.0001 and 10.56 ± 0.5813% vs 7.658 ± 0.6626%, p = 0.0025 respectively). On the contrary, the percentage of naïve B- cells was found to be significantly lower in the patients than normal controls (61.04 ± 1.691% vs 73.62 ± 1.320%, p < 0.0001). Acute rejection episodes ( n = 38) were associated with increase in peripheral percentage of total B-cells (19.02 ± 1.457 vs. 10.80 ± 0.6338, P < 0.0001) and activated B-cells (33.92 ± 1.756 vs. 23.26 ± 1.113, P < 0.0001). On the contrary, the percentage of plasma cells and memory B-cells and naïve B- cells was significantly lower during rejection episodes (0.7447 ± 0.09 vs. 2.363 ± 0.1529, P < 0.0001, 5.871 ± 0.6677 vs. 12.12 ± 0.6584, P < 0.0001 and 44.53 ± 2.504 vs. 52.61 ± 2.488, P = 0.0311 respectively). Conclusion The percentage of activated B-cells and Memory B-cells were persistently high in uremic patients suggesting that these patients are always in a stage of immune activation. Acute rejection episodes were associated with increased percentage of activated B-cells but decrease in the percentage of plasma- and memory-B cells in the peripheral blood. Therefore, post- transplantation, periodic measurements of B-cell subsets may serve as an important marker in the prediction of acute allograft rejection. [ABSTRACT FROM AUTHOR]