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lüll Change you can B(cell)eive in: recent progress confirms a critical role for B cells in type 1 diabetes O'Neill SK; Liu E; Cambier JCCurr Opin Endocrinol Diabetes Obes 2009[Aug]; 16 (4): 293-8PURPOSE OF REVIEW: 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. RECENT FINDINGS: 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. SUMMARY: 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.|Animals[MESH]|Antibodies, Monoclonal/immunology[MESH]|Antigens, CD20/metabolism[MESH]|B-Lymphocytes/cytology/*immunology[MESH]|Diabetes Mellitus, Type 1/drug therapy/*immunology/prevention & control[MESH]|Humans[MESH]|Mice[MESH]|Mice, Inbred NOD[MESH]|Sialic Acid Binding Ig-like Lectin 2/metabolism[MESH] |