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B cell depletion: a novel therapy for autoimmune diabetes?
Hélène Bour-Jordan, Jeffrey A. Bluestone
Hélène Bour-Jordan, Jeffrey A. Bluestone
Published December 3, 2007
Citation Information: J Clin Invest. 2007;117(12):3642-3645. https://doi.org/10.1172/JCI34236.
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Commentary

B cell depletion: a novel therapy for autoimmune diabetes?

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Abstract

Autoimmune diabetes is believed to be mediated primarily by T cells. However, B cells have been implicated in the pathogenesis of the disease in NOD mice. Although preclinical studies have been limited by the absence of anti-CD20 reagents that can induce B cell depletion in mice, a clinical trial using the B cell–depleting anti-CD20 monoclonal antibody rituximab (Rituxan) is underway in type 1 diabetes patients. In this issue of the JCI, Hu et al. describe the generation of transgenic NOD mice that express human CD20 on B cells (see the related article beginning on page 3857). They show that anti-CD20 therapy induces B cell depletion in these mice and offers some level of protection against diabetes. Although many questions remain unanswered, this mouse model represents the first opportunity to evaluate the potential value of rituximab as a novel therapy for autoimmune diabetes.

Authors

Hélène Bour-Jordan, Jeffrey A. Bluestone

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Figure 1

Anti-CD20 therapy and B cells in autoimmunity.

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Anti-CD20 therapy and B cells in autoimmunity.
Autoreactive B cells play...
Autoreactive B cells play a role in autoimmune diseases via their production of circulating autoantibodies and/or their role as antigen-presenting cells for autoreactive T cells after the capture of self antigens by cell surface autoantibodies that increase their antigen-presentation capabilities (i). Rituximab and other anti-CD20 mAbs cross-link CD20 on the surface of B cells and induce B cell depletion mainly through ADCC, although complement-dependent cytotoxicity (CDC) and apoptosis have also been implicated (ii). Anti-CD20–mediated B cell depletion prevents interaction with autoreactive T cells (iii) and reduces the amount of circulating autoantibodies (iv), although with much slower kinetics. Finally, as suggested by Hu et al. in their study in this issue of the JCI (1), anti-CD20 therapy may induce Treg and regulatory B cell populations (CD4+Foxp3+ Tregs and transition type 2 [T2] B cells) that could play a role in restoring immune tolerance, possibly via the production of IL-10 (v).

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