The CD19 signalling molecule is elevated in NOD mice and controls type 1 diabetes development

Plebanski, M, Ziegler, A, Le Page, M and Maxwell, M 2013, 'The CD19 signalling molecule is elevated in NOD mice and controls type 1 diabetes development', Diabetologia, vol. 56, no. 12, pp. 2659-2668.


Document type: Journal Article
Collection: Journal Articles

Title The CD19 signalling molecule is elevated in NOD mice and controls type 1 diabetes development
Author(s) Plebanski, M
Ziegler, A
Le Page, M
Maxwell, M
Year 2013
Journal name Diabetologia
Volume number 56
Issue number 12
Start page 2659
End page 2668
Total pages 10
Publisher Springer
Abstract Aims/hypothesis Type 1 diabetes is characterised by early peri-islet insulitis and insulin autoantibodies, followed by invasive insulitis and beta cell destruction. The immunological events that precipitate invasive insulitis are not well understood. We tested the hypothesis that B cells in diabetesprone NOD mice drive invasive insulitis through elevated expression of CD19 and consequent enhanced uptake and presentation of beta cell membrane-bound antigens to islet invasive T cells. Methods CD19 expression and signalling pathways in B cells from NOD and control mice were compared. Expansion of CD8+ T cells specific for insulin and islet-specific glucose-6- phosphatase catalytic subunit-related protein (IGRP) were compared in CD19-deficient and wild-type NOD mice and this was correlated with insulitis severity. The therapeutic potential of anti-CD19 treatment during the period of T cell activation was assessed for its ability to block invasive insulitis. Results CD19 expression and signalling in B cells was increased in NOD mice. CD19 deficiency significantly diminished the expansion of CD8+ T cells with specificity for the membrane-bound beta cell antigen, IGRP. Conversely the reduction in CD8+ T cells with specificity for the soluble beta cell antigen, insulin, was relatively small and not significant. Conclusions/interpretation Elevated CD19 on NOD B cells promotes presentation of the membrane-bound antigen, IGRP, mediating the expansion of autoreactive T cells specific for antigens integral to beta cells, which are critical for invasive insulitis and diabetes. Downregulating the CD19 signalling pathway in insulin autoantibody-positive individuals before the development of type 1 diabetes may prevent expansion of islet-invasive T cells and preserve beta cell mass.
Subject Immunology not elsewhere classified
Keyword(s) B cells
CD19 signalling molecule
Invasive insulitis
Membrane-bound antigen
NOD mice
T cells
Type 1 diabetes
DOI - identifier 10.1007/s00125-013-3038-2
Copyright notice © 2013 Springer-Verlag Berlin Heidelberg.
ISSN 0012-186X
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