Role of B lymphocytes in the pathogenesis of type 1 diabetes

Curr Diab Rep. 2014;14(11):543. doi: 10.1007/s11892-014-0543-8.

Abstract

Though type 1 diabetes (T1D) is considered a T cell-mediated autoimmune disorder, recent evidence indicates that B cells play a critical role in disease. This conclusion is based in part on the success of anti-CD20 (rituximab) therapy, which by broadly depleting B cells delays disease progression in non-obese diabetic (NOD) mice and new-onset patients. B cell receptor (BCR) specificity to islet autoantigen is key. NOD mice whose B cell repertoire is biased toward insulin reactivity show increased disease development, while bias away from insulin reactivity largely prevents disease. Although the operative disease-promoting B cell effector function remains undefined, islet-antigen reactive B cells function in antigen presentation to diabetogenic CD4 T cells. Other studies implicate B cells in antigen presentation to CD8 T cells. B cell participation in TID appears predicated on faulty B cell tolerance. Here, we review extant findings implicating B cells in T1D in mice and men.

Publication types

  • Review

MeSH terms

  • Animals
  • Antibodies, Monoclonal, Murine-Derived / pharmacology
  • Autoantibodies / blood*
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / pathology
  • Diabetes Mellitus, Type 1 / drug therapy
  • Diabetes Mellitus, Type 1 / immunology
  • Diabetes Mellitus, Type 1 / physiopathology*
  • Disease Progression
  • Humans
  • Immune Tolerance / drug effects
  • Immune Tolerance / immunology*
  • Immunologic Factors / pharmacology
  • Lymphocyte Depletion
  • Mice
  • Mice, Inbred NOD
  • Molecular Targeted Therapy
  • Receptors, Antigen, B-Cell / antagonists & inhibitors
  • Receptors, Antigen, B-Cell / immunology*
  • Rituximab

Substances

  • Antibodies, Monoclonal, Murine-Derived
  • Autoantibodies
  • Immunologic Factors
  • Receptors, Antigen, B-Cell
  • Rituximab