Pancreatic lymph nodes (PLN) at the periphery of the pancreas, propagate the autoimmune response and have been understudied in type 1 diabetes (T1D). The aim of this study was to analyse the structure and cellular content of secondary B cell follicles (germinal centres (GC)) in recent-onset T1D compared with matched controls.
Materials and Methods
8 PLNs from 6 donors with recent onset T1D (<1 year duration) and 10 PLNs from 8 non-diabetic donors were stained for the proliferation marker Ki67. GCs were identified based on ≥3 Ki67+ cells within a B cell follicle (CD20+ cells). The area of each PLN examined was measured with ImageJ software.
In the control group, 8 proliferating GCs were observed in 6 PLNs; each containing between 4-227 Ki67+ cells (mean 72.3±23.6). The Ki67+ GC cells accounted for 11.7-75.9% of all cells within the B cell follicle (mean 43.6±7.1%). Unexpectedly, only one proliferating GC was identified in the PLNs of the recent onset T1D group and as this was on the edge of a section and it was not possible to quantify the cells accurately. The area of the PLNs examined was not statistically different between the groups (mean 3.1±0.8 mm2 (range 0.05-6.7 mm2) and (mean 5.4±2.1 mm2 (range 0.45-15.9 mm2); p=0.2 for the T1D and control group respectively).
Germinal centre replication is required for affinity maturation of the humoral immune response. Counter-intuitively, replication is decreased in GCs in recent onset T1D compared with non-diabetic controls. These data may reflect burnout of the humoral response but this is not supported by the presence of insulitis in recent onset islets1 and post-diagnosis islet autoantibody production. Another interpretation may be attempted regulation of the autoimmune response in T1D PLNs. Further studies are required to understand the mechanisms underlying decreased Ki67+ GCs in T1D.