Contribution of autoallergy to the pathogenesis in the NOD mice

Abstract

The immunoglobulin isotype IgE is commonly associated with allergy. However, its involvement in autoimmune disease in general, and Type 1 diabetes (T1D) in particular, is still not completely clarified, nonetheless IgE has been observed in patients with T1D. In this article, we aimed to elucidate the contribution of IgE in the pathogenesis of the disease in a spontaneous model for T1D, i.e. the NOD mouse. We observed increased levels of IgE in splenic, lymph node and peripheral blood B cells in the NOD mice compared to the control C57BL/6 (B6) mice. No correlation was found between the IgE levels on B cells and those in the sera of these mice, indicating a B cell intrinsic property mediating IgE capture in NOD. Functionally, the B cells from NOD were similar to B6 in rescuing the IgE-mediated immune response via the low affinity receptor CD23 in a transgenic adoptive transfer system. However, the involvement of IgE in diabetes development was clearly demonstrated, as treatment with anti-IgE antibodies delayed the incidence of the diabetes in the NOD mice compared to the PBS treated group. Pancreas sections from a 13-week-old NOD revealed the presence of tertiary lymphoid structures with T cells, B cells, germinal centers and IgE suggesting the presence of autoantigen specific IgE. Our study provides an insight to the commonly overlooked immunoglobulin IgE and its potential role in autoimmunity.

• Autoallergy
• B lymphocytes
• IgE
• NOD mouse
• Type 1 diabetes

Acknowledgements

We would like to thank Prof. D.H Conrad for the anti-IgE producing 23G3 hybridoma cells, Prof. Birgitta Heyman and Prof. Per-Arne Oldenborg’s group for discussions, reagents and microscopy.

Declaration of interest

The authors declare no conflict of interest. This study was supported by grants from the Swedish Diabetes Foundation, The Swedish Children's Diabetes Foundation, Stiftelsen Lars Hiertas Minne, Insamlingsstiftelsen vid Umeå universitet.

Supplementary material available online.

Supplemental Figures S1 and S2