Abstract

Increasing evidence has confirmed that immunoglobulins (Igs) can be expressed in non-B cells. Our previous work demonstrated that mesangial cells and podocytes express IgA and IgG, respectively. The aim of this work was to reveal whether proximal tubular epithelial cells (PTECs) express Igs. High-throughput single-cell RNA sequencing (scRNA-seq) detected Igs in a small number of PTECs, and then we combined nested PCR with Sanger sequencing to detect the transcripts and characterize the repertoires of Igs in PTECs. We sorted PTECs from the normal renal cortex of two patients with renal cancer by FACS and further confirmed their identify by LRP2 gene expression. Only the transcripts of the IgG heavy chain were successfully amplified in 91/111 single PTECs. We cloned and sequenced 469 VHDJH transcripts from 91 single PTECs and found that PTEC-derived IgG exhibited classic VHDJH rearrangements with nucleotide additions at the junctions and somatic hypermutations. Compared with B cell-derived IgG, PTEC-derived IgG displayed less diversity of VHDJH rearrangements, predominant VH1-24/DH2-15/JH4 sequences, biased VH1 usage, centralized VH gene segment location at the 3′ end of the genome and non-Gaussian distribution of the CDR3 length. These results demonstrate that PTECs can express a distinct IgG repertoire that may have implications for their role in the renal tubular epithelial-mesenchymal transition.

Highlights

  • Increasing evidence has confirmed that immunoglobulins (Igs) can be expressed in non-B cells

  • We found for the first time that proximal tubular epithelial cells (PTECs) transcribe IgG and exhibit functional ­VHDJH rearrangements of IgG at the single-cell level

  • Similar to B-IgG, PTEC-derived IgG showed classic V­ HDJH rearrangements with nucleotide insertions at junctions and somatic hypermutation concentrated in the complementary determining region (CDR)

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Summary

Introduction

Increasing evidence has confirmed that immunoglobulins (Igs) can be expressed in non-B cells. Compared with B cell-derived IgG, PTEC-derived IgG displayed less diversity of ­VHDJH rearrangements, predominant VH1-24/DH2-15/JH4 sequences, biased VH1 usage, centralized VH gene segment location at the 3′ end of the genome and non-Gaussian distribution of the CDR3 length. These results demonstrate that PTECs can express a distinct IgG repertoire that may have implications for their role in the renal tubular epithelial-mesenchymal transition. The expression of Igs has been thought to be exclusive to B cells This theory has been challenged over the past decade by increasing evidence reporting that Igs could be expressed in non-B cells. Natural antibodies in skin and ­mucosa[19,20] and as growth factors to promote cell proliferation and adhesion as well as promote initiation and metastasis of cancer by binding to integrins as extracellular matrix p­ rotein[7]

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