Neuromyelitis Spectrum Disorder (NMOSD)

In our most recent study, we explored both B cell tolerance and the origins of pathogenic autoantibodies in NMOSD. We demonstrated that the B cell tolerance checkpoints, which normally function to counter-select autoreactive B cells during the development of the naive B cells repertoire, are defective in NMOSD. The consequence is an abnormally high load of self-reactive naive B cells. We then demonstrated that pathogenic aquaporin autoantibodies that define the disease can ascend from this aberrant formed population of naive B cells. These findings demonstrate fundamental defects of B cell tolerance in NMOSD and reveal a mechanism by which AQP4 autoantibodies develop. The study also further highlights the divergent roles of B cells in MS and NMOSD.

Cotzomi, E., Stathopoulos, P., Lee, C.S., Ritchie, A.M., Soltys, J.N., Delmotte, F.R., Oe, T., Sng, J., Jiang, R., Ma, A.K., Vander Heiden, J.A., Kleinstein, S.H., Levy, M., Bennett, J.L., Meffre, E., and O'Connor, K.C. (2019). Early B cell tolerance defects in neuromyelitis optica favour anti-AQP4 autoantibody production. Brain, 142(6):1598-1615.

Meffre, E., and O'Connor, K.C. (2019). Impaired B-cell tolerance checkpoints promote the development of autoimmune diseases and pathogenic autoantibodies. Immunol Rev., 292(1):90-101.

Bennett, J.L., O'Connor, K.C., Bar-Or, A., Zamvil, S.S., Hemmer, B., Tedder, T.F., von Budingen, H.C., Stuve, O., Yeaman, M.R., Smith, T.J., and Stadelmann, C. (2015). B lymphocytes in neuromyelitis optica. Neurol Neuroimmunol Neuroinflamm, 2(3):e104. PMCID: PMC4426682.