T-cell receptor and B-cell receptor repertoires profiling in pleural tuberculosis

Front Immunol. 2024 Nov 27:15:1473486. doi: 10.3389/fimmu.2024.1473486. eCollection 2024.

Abstract

Background: Tuberculosis (TB) is a leading cause of death worldwide from a single infectious agent. In China the most common extra-pulmonary TB (EPTB) is pleural tuberculosis (PLTB). An important clinical feature of PLTB is that the lymphocytes associated with TB will accumulate in the pleural fluid. The adaptive immune repertoires play important roles in Mycobacterium tuberculosis (Mtb) infection.

Methods: In this study, 10 PLTB patients were enrolled, and their Peripheral Blood Mononuclear Cells(PBMCs) and Pleural Effusion Mononuclear Cells(PEMCs) were collected. After T cells were purified from PBMCs and PEMCs, high-throughput immunosequencing of the TCRβ chain (TRB), TCRγ chain(TRG), and B cell receptor(BCR) immunoglobulin heavy chain (IGH) were conducted on these samples.

Results: The TRB, TRG, and BCR IGH repertoires were characterized between the pleural effusion and blood in PLTB patients, and the shared clones were analyzed and collected. The binding activity of antibodies in plasma and pleural effusion to Mtb antigens was tested which indicates that different antibodies responses to Mtb antigens in plasma and pleural effusion in PLTB patients. Moreover, GLIPH2 was used to identify the specificity groups of TRB clusters and Mtb-specific TRB sequences were analyzed and collected by VJ mapping.

Conclusion: We characterize the adaptive immune repertoires and identify the shared clones and Mtb-specific clones in pleural effusion and blood in PLTB patients which can give important clues for TB diagnosis, treatment, and vaccine development.

Keywords: B cell receptor; T cell receptor; antibody; deep sequencing; pleural tuberculosis.

MeSH terms

  • Adult
  • Aged
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism
  • Female
  • Humans
  • Male
  • Middle Aged
  • Mycobacterium tuberculosis* / immunology
  • Receptors, Antigen, B-Cell* / genetics
  • Receptors, Antigen, B-Cell* / immunology
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / immunology
  • Receptors, Antigen, T-Cell / metabolism
  • Tuberculosis, Pleural* / diagnosis
  • Tuberculosis, Pleural* / immunology

Substances

  • Receptors, Antigen, B-Cell
  • Receptors, Antigen, T-Cell

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the China Postdoctoral Science Foundation (Project No: 2017M620052); The National Natural Science Foundation of China (32070937); the 2115 Talent Development Program of China Agricultural University (00109029); The ImmuQuad Young Scholar Grant to HL.