Review

B cells in type 1 diabetes mellitus and diabetic kidney disease

  • Nature Reviews Nephrology 13, 712720 (2017)
  • doi:10.1038/nrneph.2017.138
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Abstract

Type 1 diabetes mellitus (T1DM) is an autoimmune disorder that affects an estimated 30 million people worldwide. It is characterized by the destruction of pancreatic β cells by the immune system, which leads to lifelong dependency on exogenous insulin and imposes an enormous burden on patients and health-care resources. T1DM is also associated with an increased risk of comorbidities, such as cardiovascular disease, retinopathy, and diabetic kidney disease (DKD), further contributing to the burden of this disease. Although T cells are largely considered to be responsible for β-cell destruction in T1DM, increasing evidence points towards a role for B cells in disease pathogenesis. B cell-depletion, for example, delays disease progression in patients with newly diagnosed T1DM. Loss of tolerance of islet antigen-reactive B cells occurs early in disease and numbers of pancreatic CD20+ B cells correlate with β-cell loss. Although the importance of B cells in T1DM is increasingly apparent, exactly how these cells contribute to disease and its comorbidities, such as DKD, is not well understood. Here we discuss the role of B cells in the pathogenesis of T1DM and how these cells are activated during disease development. Finally, we speculate on how B cells might contribute to the development of DKD.

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Author information

Affiliations

  1. Department of Immunology and Microbiology, University of Colorado School of Medicine, 12800 E 19th Avenue, RC1 North, P18–8100, Aurora, Colorado 80045–2537, USA.

    • Mia J. Smith
    •  & John C. Cambier
  2. Department of Microbiology, Immunology, and Pathology, Colorado State University, 1682 Campus Delivery, Fort Collins, Colorado 80523–1682, USA.

    • Mia J. Smith
  3. Barbara Davis Center for Childhood Diabetes, University of Colorado School of Medicine, 1775 Aurora Court, Aurora, Colorado 80045–2537, USA.

    • Kimber M. Simmons

Authors

  1. Search for Mia J. Smith in:

  2. Search for Kimber M. Simmons in:

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Contributions

All authors researched the data for the article, discussed the content, wrote the article and reviewed and/or edited the manuscript before submission.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to John C. Cambier.

Glossary

Germinal centre reaction

The anatomical site in which B cells and T cells respond collaboratively to immunogen, leading to B cell proliferation, somatic Ig gene mutation, affinity maturation and immunoglobulin class switch recombination.

Anergy

A mode of B cell tolerance characterized by unresponsiveness to antigenic stimulation, including the inability to become activated, proliferate and secrete antibody.

Diabetogenic T cells

T cells that can cause diabetes, such as insulin-reactive T cells.

Cross-presenting

The process by which antigen presenting cells process and present extracellular antigens to CD8+ T cells.

High-affinity anti-insulin antibodies

Antibodies with an affinity for insulin >10−9 mol/l.

Plasma cells

Terminally differentiated B cells that secrete antibody.

Recombining sequence rearrangements

DNA rearrangements that delete one or both Ig κ genes, leading to expression of Ig λ light chains.

λ-Immunoglobulin light chain-positive B cells

B cells that express λ light chains as a component of their B cell antigen receptor; high levels of these cells is indicative of increased receptor editing.

Insulitis

Inflammation of the pancreas due to infiltration of lymphocytes.

Haplotypes

A set of genes inherited from a single parent.

Antibody-dependent cell-mediated cytotoxicity

The process by which an effector cell of the immune system, such as a natural killer cell, targets a cell for lysis based on the presence of antibodies that are bound to surface antigens on the target cell.

Mixed meal tolerance test

An assay to determine the amount of insulin an individual produces; the individual consumes a drink containing a mixture of protein, fat, and carbohydrates that stimulates the release of insulin from pancreatic β cells; blood is drawn several times over a period of hours and assayed for C-peptide, which reflects endogenous insulin production.