Role of B Lymphocytes in the Pathogenesis of Type 1 Diabetes

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.