Immune Repertoire Profiling Reveals that Clonally Expanded B and T Cells Infiltrating Diseased Human Kidneys Can Also Be Tracked in Blood.

Johannes Weinberger,Richard Weiss,Christian Gabriel,Martin Danzer,Susanne Suessner,Roman Reindl-Schwaighofer,Judith Sunzenauer,Susanne Schaller,Raul Jimenez-Heredia,Stephan Winkler,Rainer Oberbauer,Grant Lythe

doi:10.1371/journal.pone.0143125

Abstract

Recent advances in high-throughput sequencing allow for the competitive analysis of the human B and T cell immune repertoire. In this study we compared Immunoglobulin and T cell receptor repertoires of lymphocytes found in kidney and blood samples of 10 patients with various renal diseases based on next-generation sequencing data. We used Biomed-2 primer panels and ImmunExplorer software to sequence, analyze and compare complementarity determining regions and V-(D)-J elements. While generally an individual’s renal receptor repertoire is different from the repertoire present in blood, 94% (30/32) of the lymphocytes with clonal expansion in kidney can also be traced in blood however, not all of these clonotypes are equally abundant. Summarizing the data of all analyzed patients, 68% of highly expanded T cell clonotypes and 30% of the highly expanded B cell clonotypes that have infiltrated the kidney can be found amongst the five most abundant clonotypes in blood. In addition, complementarity determining region 3 sequences of the immunoglobulin heavy chains are on average more diverse than T cell receptor beta chains. Immune repertoire analysis of tissue infiltrating B and T cells adds new approaches to the assessment of adaptive immune response in kidney diseases. Our data suggest that expanded clonotypes in the tissues might be traceable in blood samples in the course of treatment or the natural history of the disease.

Highlights

The adaptive immune system shields the human body from a large variety of potential pathogens
After isolating B and T lymphocytes from renal tissue samples and peripheral blood, we applied high-throughput sequencing on the rearranged V-(D)-J regions to assess IG and T cell receptor (TR) clonality and diversity of the B and T cell repertoire in both compartments
We identified a total of 613 036 different clonotypes in blood samples (252 443 B cell clonotypes and 360 593 T cell clonotypes) as well as 261 280 distinct clonotypes in the tissue samples (154 670 and 106 610 for B and T cell clonotypes, respectively)

Summary

Introduction

The adaptive immune system shields the human body from a large variety of potential pathogens This protection is mediated by B and T lymphocytes and their receptors that bind pathogen derived antigens as well as major histocompatibility complex (MHC) bound peptides. Apart from receptor specificity, B and T cells can differentiate into several cell subtypes covering a wide range of different tasks. Besides their potential to differentiate into antibody secreting plasma cells, B cells can function as antigen-presenting or immune-regulatory cells [3]. T helper cells (CD4+) conduct the immunological response via cytokine release and cytotoxic T cells (CD8+) directly attack cells presenting foreign antigens via MHC-I.[5, 6] According to the clonal theory of adaptive immunity, antigen recognition through specific B or T cell receptors results in the clonal expansion of all antigen specific lymphocyte subtypes thereby explaining the highly dynamic nature of B and T cell diversity

Methods

Results

Conclusion