To B or Not to B: (Anti)bodies of Evidence on the Crime Scene of Type 1 Diabetes?

摘要

Although autoantibodies (auto-Abs) against β-cell antigens helped in denning type 1 diabetes as an autoimmune disease and are invaluable bio-markers, their pathogenic role is unclear. Studies in nonobese diabetic (NOD) mice devoid of B cells (Igμ~(null) or treated with anti-μ Abs) suggest that B cells are necessary for the disease to develop (1,2). The critical role of B cells in this process is thought to be linked to their antigen-presenting function through major histocompati-bility class II molecules, as NOD mice harboring I-Ag7-deficient B cells are also protected from diabetes (3). The capacity of B cells to efficiently uptake β-cell antigens through surface Ig is critical to this function, as inhibiting this Ig-mediated uptake abolishes the β-cell antigen-presenting function of B cells in vitro (4), while transgenic manipulation of the Ig specificity in NOD mice impacts on diabetes incidence (5). Thus, autoreactive B cells may be exquisitely efficient in capturing and presenting self antigens, leading to autoimmune T-cell activation. In a therapeutic perspective, treatment with depleting anti-CD20 Abs delays and reduces diabetes onset in NOD mice and is even capable of reversing established disease (6). These findings have been successfully translated into human clinical trials (7).