058 – Characterizing IgA+ plasma cell-mediated protection at the T cell effector stage of experimental autoimmune encephalomyelitis

Printed Poster | Session 2

058 – Characterizing IgA+ plasma cell-mediated protection at the T cell effector stage of experimental autoimmune encephalomyelitis

Angela Wang (1) – Karen Yeung (1) – Olga Rojas (1) – Valeria Ramaglia (1) – Jennifer Gommerman (1)
University of Toronto, Department of Immunology, Toronto, Canada (1)


B cell depletion therapy is an effective treatment for relapse-remitting Multiple Sclerosis. Anti-CD20 treatment, however, does not impact the plasma cell (PC) compartment, and oligoclonal antibody bands in the cerebrospinal fluid remain unchanged in patients who have had a positive clinical response to anti-CD20. In contrast, combined depletion of both B cells and antibody-secreting PC leads to exacerbated MS symptoms, suggesting a possible role for PCs in disease regulation. Our lab and others have demonstrated critical roles for cytokine production by PCs in regulating Experimental Autoimmune Encephalomyelitis (EAE), the animal model of MS. Specifically, we find that intestine-derived PCs can migrate into the inflamed CNS and attenuate EAE in a manner that is dependent on the anti-inflammatory cytokine IL-10. Here, I hypothesize that regulatory IgA+ PCs offer protection locally within the central nervous system (CNS) during the T cell effector phase of EAE by modulating the inflammatory cell types of the CNS. To answer this, I have used an adoptive transfer EAE approach to separate T cell priming versus effector events. I assessed the impact of encephalogenic CD4+ T cells transferred into WT recipient mice versus BAFF-transgenic (BAFF-Tg) recipient mice which have an overabundance of IgA+ PCs. Compared to WT recipient mice, BAFF-Tg recipient mice that received encephalogenic donor CD4+ T cells were protected from developing severe EAE. Protection was correlated with a lower frequency of cytokine-producing CD4+ T cells, less inflammation and demyelination, and the presence of IgA-secreting cells in the CNS. I also observed a decrease in the number of IgA+ and CD138+ cells in the small intestine of recipient mice compared to naïve mice, suggesting that inflammation may prompt IgA+ PC migration out of the gut independent of effects from immunization adjuvants. Ongoing work is directed towards adoptive transfer experiments into PC-deficient Cd19crePrdm1fl/fl mice where we expect increased EAE severity, and to identify the target cell types for IgA+ PC-derived IL-10 regulation within the CNS during inflammation.