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Diabetologia. 2018 Aug;61(8):1794-1803. doi: 10.1007/s00125-018-4651-x. Epub 2018 Jun 7.

Loss of CXCR3 expression on memory B cells in individuals with long-standing type 1 diabetes.

Author information

1
Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff, CF14 4XN, UK.
2
Diabetes Research Unit Cymru, Swansea University, Swansea, UK.
3
Division of Population Medicine, Cardiff University School of Medicine, Cardiff, UK.
4
Section of Endocrinology, Yale University School of Medicine, New Haven, CT, USA.
5
Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff, CF14 4XN, UK. wongfs@cardiff.ac.uk.

Abstract

AIMS/HYPOTHESIS:

Islet-specific autoantibodies can predict the development of type 1 diabetes. However, it remains unclear if B cells, per se, contribute to the causal pancreatic immunopathology. We aimed to identify phenotypic signatures of disease progression among naive and memory B cell subsets in the peripheral blood of individuals with type 1 diabetes.

METHODS:

A total of 69 participants were recruited across two separate cohorts, one for discovery purposes and the other for validation purposes. Each cohort comprised two groups of individuals with type 1 diabetes (one with newly diagnosed type 1 diabetes and the other with long-standing type 1 diabetes) and one group of age- and sex-matched healthy donors. The phenotypic characteristics of circulating naive and memory B cells were investigated using polychromatic flow cytometry, and serum concentrations of various chemokines and cytokines were measured using immunoassays.

RESULTS:

A disease-linked phenotype was detected in individuals with long-standing type 1 diabetes, characterised by reduced C-X-C motif chemokine receptor 3 (CXCR3) expression on switched (CD27+IgD-) and unswitched (CD27intermediateIgD+) memory B cells. These changes were associated with raised serum concentrations of B cell activating factor and of the CXCR3 ligands, chemokine (C-X-C motif) ligand (CXCL)10 and CXCL11. A concomitant reduction in CXCR3 expression was also identified on T cells.

CONCLUSIONS/INTERPRETATION:

Our data reveal a statistically robust set of abnormalities that indicate an association between type 1 diabetes and long-term dysregulation of a chemokine ligand/receptor system that controls B cell migration.

KEYWORDS:

Autoimmunity; B cells; B220; BAFF; CD24; CD95; CXCL10; CXCL11; CXCR3; Type 1 diabetes

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