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Yale IBIO investigators link tolerance defects to pathogenic autoantibody production

June 21, 2019

A team led by IBIO faculty members, Eric Meffre and Kevin O’Connor, explored both B cell tolerance and the origins of pathogenic autoantibodies in neuromyelitis optica (NMO), a severe autoimmune neurological disease that primarily affects young women, published in Brain: A Journal of Neurology. They demonstrated that the B cell tolerance checkpoints, which normally function to counter-select autoreactive B cells during their development, are defective in NMO. The consequence of which is an abnormally high load of self-reactive B cells. They then demonstrated that pathogenic, aquaporin water channel-specific autoantibodies can rise from this aberrantly formed reservoir of self-reactive B cells. Overall, the findings demonstrate fundamental defects of B cell tolerance in NMO and reveal a mechanism by which autoantibodies develop.

In addition, they were very pleased to have been selected for the cover illustration. They worked with a very talented Yale student, Sonia Ruiz, who created the image. The image has a number of interesting design elements. The optic nerve and spinal cord are “built” from autoantibodies reflecting their deposition on these components of the central nervous system (CNS). The doorway represents the trafficking of the B cells to the CNS and they highlight our report, regarding how these B cells breach an unchecked tolerance “gate” in NMOSD. Finally, the cutaway of the face is a composite of smaller images that include, autoantibodies, B cells, oligodendrocytes and the aquaporin water channel.

Find article here:

https://academic.oup.com/brain/article/142/6/1598/5485817