Change you can B(cell)eive in: recent progress confirms a critical role for B cells in type 1 diabetes.
OBJECTIVE
Here we review extant recent findings regarding the multiple roles of B cells in type 1 diabetes (T1D) and discuss how autoreactive B cells may become activated by a breach in B cell tolerance, and thereby initiate disease. Finally, we discuss the use of B cell-targeted therapies for treatment of autoimmunity.


RESULTS
Anti-CD20-specific depletion of B cells prevents and reverses diabetes in human CD20/non-obese diabetic (NOD) mice. Correspondingly, in nontransgenic NOD mice, B cells are effectively depleted with high dose antimouse CD20 mAbs of varying isotypes, and this also prevents diabetes in more than 60% of the mice when administered early, and significantly delays disease in 15-week-old animals. A separate study revealed that targeting B cells with anti-CD22/cal monoclonal antibody therapy delays diabetes onset in prediabetic NOD mice and restores normoglycemia in new-onset hyperglycemic NOD mice. In humans, a clinical trial of rituximab in new onset type 1 diabetics has yielded promising preliminary findings.


CONCLUSIONS
B cells are major players in T1D in humans, and clearly essential for disease development in the NOD mouse model of T1D. In this review, we discuss the silencing of autoreactive B cells and how failure of this process may contribute to autoimmunity. Further, we describe the most recent advances in studies of therapeutic effects of B cell depletion in T1D, and provide recent data indicating the diverse functions by which B cells may mediate disease.
O'Neill
Shannon K
SK
University of Colorado Denver and National Jewish Health, 1400 Jackson Street, Denver, Colorado 80206, USA.
Liu
Edwin
E
Cambier
John C
JC
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D018951:Antigens, CD20 / Q000378:metabolism; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy / Q000276:immunology* / Q000517:prevention & control; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D051918:Sialic Acid Binding Ig-like Lectin 2 / Q000378:metabolism
D000911:Antibodies, Monoclonal; D018951:Antigens, CD20; D051918:Sialic Acid Binding Ig-like Lectin 2