Journal Article

Myelin-reactive B cells exacerbate CD4+ T cell-driven CNS autoimmunity in an IL-23-dependent manner

Pereira, Resel, Mailhot, Benoit, Baillargeon, Joanie, Droit, Arnaud, Fudge, Neva, Joly-Beauparlant, Charles, Fazazi, Mohamed Reda, Moore, Craig S., Regmi, Aryan, Grenier, Philippe, Yeola, Asmita Pradeep, Bertrand, Nicolas, Doss, Prenitha Mercy Ignatius Arokia, Lacroix, Steve, Akbar, Irshad, Rojas, Olga L., Rangachari, Manu

2024

Overview

B cells and T cells collaborate in multiple sclerosis (MS) pathogenesis. IgH [MOG] mice possess a B cell repertoire skewed to recognize myelin oligodendrocyte glycoprotein (MOG). Here, we show that upon immunization with the T cell-obligate autoantigen, MOG [35-55] , IgH [MOG] mice develop rapid and exacerbated experimental autoimmune encephalomyelitis (EAE) relative to wildtype (WT) counterparts, characterized by aggregation of T and B cells in the IgH [MOG] meninges and by CD4 + T helper 17 (Th17) cells in the CNS. Production of the Th17 maintenance factor IL-23 is observed from IgH [MOG] CNS-infiltrating and meningeal B cells, and in vivo blockade of IL-23p19 attenuates disease severity in IgH [MOG] mice. In the CNS parenchyma and dura mater of IgH [MOG] mice, we observe an increased frequency of CD4 + PD-1 + CXCR5 - T cells that share numerous characteristics with the recently described T peripheral helper (Tph) cell subset. Further, CNS-infiltrating B and Tph cells from IgH [MOG] mice show increased reactive oxygen species (ROS) production. Meningeal inflammation, Tph-like cell accumulation in the CNS and B/Tph cell production of ROS were all reduced upon p19 blockade. Altogether, MOG-specific B cells promote autoimmune inflammation of the CNS parenchyma and meninges in an IL-23-dependent manner. B cells are crucial in multiple sclerosis (MS) pathology but the mechanisms are incompletely understood. In a mouse model of MS, the authors show that B cells make IL-23, and that IL-23 invokes meningeal inflammation and CNS presence of T peripheral helper cells.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 13/31 / 14/19 / 38/91 / 631/250/38 / 631/378/1689/1666 / 64/60 / 692/420/2780/2152/1566/2493 / Animals / Autoimmune diseases / Autoimmunity / Autoimmunity - immunology / B-Lymphocytes - immunology / CD4 antigen / CD4-Positive T-Lymphocytes - immunology / Central Nervous System - immunology / CXCR5 protein / Dura mater / Encephalomyelitis, Autoimmune, Experimental - immunology / Experimental allergic encephalomyelitis / Female / Glycoproteins / Heavy chains / Helper cells / Humanities and Social Sciences / Immunization / Immunoglobulins / Inflammation / Interleukin 23 / Interleukin-23 - immunology / Interleukin-23 - metabolism / Lymphocytes / Lymphocytes B / Lymphocytes T / Meninges / Meninges - immunology / Meninges - pathology / Mice / Mice, Inbred C57BL / multidisciplinary / Multiple sclerosis / Multiple Sclerosis - immunology / Myelin / Myelin Sheath - immunology / Myelin Sheath - metabolism / Myelin-Oligodendrocyte Glycoprotein - immunology / Oligodendrocyte-myelin glycoprotein / Parenchyma / Pathogenesis / PD-1 protein / Reactive oxygen species / Science / Science (multidisciplinary) / Th17 Cells - immunology