Critical role of activation induced cytidine deaminase in Experimental Autoimmune Encephalomyelitis

Abstract

Multiple Sclerosis (MS) is a neurodegenerative autoimmune disorder caused by chronic inflammation and demyelination within the central nervous system (CNS). Clinical studies in MS patients have demonstrated efficacy with B cell targeted therapies such as anti-CD20. However, the exact role that B cells play in the disease process is unclear. Activation Induced cytidine deaminase (AID) is an essential enzyme for the processes of antibody affinity maturation and isotype switching. To evaluate the impact of affinity maturation and isotype switching, we have interrogated the effect of AID-deficiency in an animal model of MS. Here, we show that the severity of experimental autoimmune encephalomyelitis (EAE) induced by the extracellular domain of human myelin oligodendrocyte glycoprotein (MOG1-125) is significantly reduced in Aicda deficient mice, which, unlike wild-type mice, lack serum IgG to myelin associated antigens. MOG specific T cell responses are comparable between wild-type and Aicda knockout mice suggesting an active role for antigen experienced B cells. Thus affinity maturation and/or class switching are critical processes in the pathogenesis of EAE.

Keywords::

• AID
• EAE
• MS
• affinity maturation
• Isotype switching

Acknowledgement

We thank Robert Schwingendorf, Ben Grellman and Vida Asghari for genotyping of animals and managing the mice colonies.

Declaration of interest: All the authors are the employees of Genentech, a wholly owned subsidiary of Roche. The authors declare no competing financial interests. The authors are responsible for the content and the writing of this paper.