title: Germinal centre frequency is decreased in pancreatic lymph nodes from individuals with recent-onset type 1 diabetes.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Diabetes and Metabolism, Level 2 Learning and Research, University of Bristol, Southmead Hospital, Bristol, BS10 5NB, UK.
authors.forename: Abby
authors.initials: A
authors.lastname: Willcox
authors.affiliation: Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, UK.
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Richardson
authors.affiliation: Institute of Immunity and Transplantation, UCL Division of Infection and Immunity, Royal Free Campus, London, UK.
authors.forename: Lucy S K
authors.initials: LSK
authors.lastname: Walker
authors.affiliation: Division of Diabetes, Department of Medicine, Diabetes Center of Excellence, University of Massachusetts Medical School, Worcester, MA, USA.
authors.forename: Sally C
authors.initials: SC
authors.lastname: Kent
authors.affiliation: Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, UK.
authors.forename: Noel G
authors.initials: NG
authors.lastname: Morgan
authors.affiliation: Diabetes and Metabolism, Level 2 Learning and Research, University of Bristol, Southmead Hospital, Bristol, BS10 5NB, UK. K.M.Gillespie@bristol.ac.uk.
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Gillespie
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D001323:Autoantibodies / Q000276:immunology; D001324:Autoantigens / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003713:Dendritic Cells / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000378:metabolism; D005260:Female; D018858:Germinal Center / Q000276:immunology*; D006041:Goats; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000378:metabolism; D007515:Islets of Langerhans / Q000378:metabolism; D019394:Ki-67 Antigen / Q000378:metabolism; D008198:Lymph Nodes / Q000276:immunology* / Q000473:pathology*; D008297:Male; D051379:Mice; D008856:Microscopy, Fluorescence; D010179:Pancreas / Q000473:pathology*; D010641:Phenotype; D011817:Rabbits; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D007328:Insulin; D019394:Ki-67 Antigen
keywords: Histology; Islet autoimmunity; Pancreatic lymph nodes; Type 1 diabetes