3D investigation shows walls and wall-like structures around human germinal centres, probably regulating T- and B-cell entry and exit

PLoS One. 2020 Nov 10;15(11):e0242177. doi: 10.1371/journal.pone.0242177. eCollection 2020.

Abstract

This study deals with 3D laser investigation on the border between the human lymph node T-zone and germinal centre. Only a few T-cells specific for antigen selected B-cells are allowed to enter germinal centres. This selection process is guided by sinus structures, chemokine gradients and inherent motility of the lymphoid cells. We measured gaps and wall-like structures manually, using IMARIS, a 3D image software for analysis and interpretation of microscopy datasets. In this paper, we describe alpha-actin positive and semipermeable walls and wall-like structures that may hinder T-cells and other cell types from entering germinal centres. Some clearly defined holes or gaps probably regulate lymphoid traffic between T- and B-cell areas. In lymphadenitis, the morphology of this border structure is clearly defined. However, in case of malignant lymphoma, the wall-like structure is disrupted. This has been demonstrated exemplarily in case of angioimmunoblastic T-cell lymphoma. We revealed significant differences of lengths of the wall-like structures in angioimmunoblastic T-cell lymphoma in comparison with wall-like structures in reactive tissue slices. The alterations of morphological structures lead to abnormal and less controlled T- and B-cell distributions probably preventing the immune defence against tumour cells and infectious agents by dysregulating immune homeostasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • B-Lymphocytes / pathology
  • Germinal Center / pathology*
  • Humans
  • Imaging, Three-Dimensional / methods*
  • Immunoblastic Lymphadenopathy / pathology*
  • Lymphadenitis / pathology*
  • Lymphoma / pathology*
  • T-Lymphocytes / pathology

Grants and funding

funded by: BMBF, COMPLS2-087: Machine learning driven multidimensional imaging analysis of reactive and neoplastic lymph nodes-Patho234. And by the Control-T consortium, Grants HA1284/7-2. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.