Expansion and Somatic Hypermutation of B-cell Clones in Rejected Human Kidney Grafts

Abstract

Background B cell infiltrates are common in rejected kidney allografts, yet their composition is still unclear. The aim of our study was to characterize the clonal composition of B cell infiltrates of rejected human kidney grafts. Methods We used a molecular approach to characterize the partial B cell repertoires of 5 failed human kidney grafts with detectable B cell infiltrates. A comparison between the intragraft and blood repertoire was also conducted for one case. Results Redundant sequences were observed in both blood and graft, although the level of clonal amplification was significantly higher for the graft. Somatic hypermutations (SHM) were also more frequent in sequences found in the graft compared to the blood. The rate of non-silent mutations was significantly higher in complementarity determining regions (CDR) compared to framework regions in blood sequences as well as in graft sequences found at low frequency. In contrast, this preferential distribution was lost in sequences found at high frequency in the graft, suggesting a lack of affinity maturation in situ. Lastly, follicular dendritic cells were undetectable in CD20+ infiltrates in all samples examined. Conclusions We provide here evidence that B cell clones expand and undergo SHM in situ. However, the even distribution of non-silent SHM in high frequency graft sequences together with the absence of FDC do not support the view that infiltrating B cells are part of functional germinal centers.

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Targeting B Cells and Plasma Cells in Glomerular Diseases: Translational Perspectives

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New insights on innate B‐cell immunity in transplantation

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