Emerging roles for B lymphocytes in Type 1 diabetes

Abstract

Self-reactive B lymphocytes play two main pathological roles in autoimmune diseases: as secretors of autoantibodies and as specialized antigen-presenting cells that present self-components to autoreactive T lymphocytes. In recognition of these roles, recent clinical trials have utilized B-lymphocyte-depleting monoclonal antibodies to treat various autoimmune diseases, with encouraging results in those where humoral autoimmunity is clearly important. Surprisingly, recent results in animal models suggest that B-lymphocyte depletion may also be effective in the treatment of T-lymphocyte-mediated autoimmune diseases, such as Type 1 diabetes (T1D). This article reviews the experimental evidence that has uncovered pathogenic as well as regulatory roles for B lymphocytes in the prodrome of T1D and how this information is being used to develop novel therapeutic strategies to treat the disease.

Keywords::

• antigen-presenting cell
• autoantibody
• autoimmunity
• B cell
• immune tolerance
• NOD mouse
• susceptibility gene
• Type 1 diabetes

Acknowledgements

The authors are grateful to Professor Tony Basten for his insightful discussion and critical review of the manuscript.

Financial & competing interests disclosure

Pablo A Silveira is supported by grants from the National Health and Research Medical Council of Australia and the Juvenile Diabetes Research Foundation. S Lewis Cox is supported by an Australian postgraduate award. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.