Germinal centre frequency is decreased in pancreatic lymph nodes from individuals with recent-onset type 1 diabetes

Diabetologia. 2017 Jul;60(7):1294-1303. doi: 10.1007/s00125-017-4221-7. Epub 2017 Feb 17.

Abstract

Aims/hypothesis: Pancreatic lymph nodes (PLNs) are critical sites for the initial interaction between islet autoantigens and autoreactive lymphocytes, but the histology of PLNs in tissue from individuals with type 1 diabetes has not been analysed in detail. The aim of this study was to examine PLN tissue sections from healthy donors compared with those at risk of, or with recent-onset and longer-duration type 1 diabetes.

Methods: Immunofluorescence staining was used to examine PLN sections from the following donor groups: non-diabetic (n=15), non-diabetic islet autoantibody-positive (n=5), recent-onset (≤1.5 years duration) type 1 diabetes (n=13), and longer-duration type 1 diabetes (n=15). Staining for CD3, CD20 and Ki67 was used to detect primary and secondary (germinal centre-containing) follicles and CD21 and CD35 to detect follicular dendritic cell networks.

Results: The frequency of secondary follicles was lower in the recent-onset type 1 diabetes group compared with the non-diabetic control group. The presence of insulitis (as evidence of ongoing beta cell destruction) and diagnosis of type 1 diabetes at a younger age, however, did not appear to be associated with a lower frequency of secondary follicles. A higher proportion of primary B cell follicles were observed to lack follicular dendritic cell networks in the recent-onset type 1 diabetes group.

Conclusions/interpretation: Histological analysis of rare PLNs from individuals with type 1 diabetes suggests a previously unrecognised phenotype comprising decreased primary B cell follicle frequency and fewer follicular dendritic cell networks in recent-onset type 1 diabetes.

Keywords: Histology; Islet autoimmunity; Pancreatic lymph nodes; Type 1 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Animals
  • Autoantibodies / immunology
  • Autoantigens / immunology
  • B-Lymphocytes / cytology*
  • Child
  • Child, Preschool
  • Cohort Studies
  • Dendritic Cells / metabolism
  • Diabetes Mellitus, Type 1 / immunology*
  • Diabetes Mellitus, Type 1 / metabolism
  • Female
  • Germinal Center / immunology*
  • Goats
  • Humans
  • Image Processing, Computer-Assisted
  • Insulin / metabolism
  • Insulin-Secreting Cells / metabolism
  • Islets of Langerhans / metabolism
  • Ki-67 Antigen / metabolism
  • Lymph Nodes / immunology*
  • Lymph Nodes / pathology*
  • Male
  • Mice
  • Microscopy, Fluorescence
  • Pancreas / pathology*
  • Phenotype
  • Rabbits
  • Young Adult

Substances

  • Autoantibodies
  • Autoantigens
  • Insulin
  • Ki-67 Antigen