Multi-Omic Profiling of T Cell-Mediated Rejection After Kidney Transplantation Reveals B Cell Receptor Repertoire Expansion and Its Prognostic Relevance.

This study explores the immune repertoire landscape of B cell receptor (BCR) in renal allografts with T cell-mediated rejection (TCMR) to identify new therapeutic targets due to the limitations of current immunosuppressive treatments. BCR repertoires were constructed from both bulk and single-cell RNA-seq data utilizing the TRUST4 algorithm. The study revealed a significant expansion of the BCR repertoire, particularly Immunoglobulin G in TCMR compared to stable renal function across three independent renal transplant cohorts. By integrating multi-omics data from various datasets including bulk transcriptomic data, single-cell transcriptome profiles, cell line data, and immunofluorescence of renal allograft biopsies, the infiltrated plasma cell was identified as the primary holder of BCRs in renal allografts with TCMR, serving as an independent risk factor for prognosis. Additionally, MEI1 was discovered as a novel BCR-related key gene in TCMR, upregulated during plasma cell maturation and contributing to antibody secretion. This study first delineated the BCR repertoire landscape in TCMR, highlighting the crucial role of BCR, allograft-infiltrated plasma cells, and MEI1 in TCMR, thus offering novel therapeutic targets for improving allograft outcomes.