Title :

A Spontaneous Model of Experimental Autoimmune Encephalomyelitis Provides Evidence of MOG-Specific B Cell Recruitment and Clonal Expansion.

Author(s) :

Salvador, Florent [Auteur]
Lille Neurosciences & Cognition - U 1172 [LilNCog]
Deramoudt, Laure [Auteur]
Lille Neurosciences & Cognition - U 1172 [LilNCog]
Leprêtre, Frédéric [Auteur]
Genomic @ Lille - PLBS [GO@L]
Figeac, Martin [Auteur]
Genomic @ Lille - PLBS [GO@L]
Guerrier, Thomas [Auteur]
Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286
Boucher, Julie [Auteur]
Lille Neurosciences & Cognition - U 1172 [LilNCog]
Bas, Mathilde [Auteur]
Lille Neurosciences & Cognition - U 1172 [LilNCog]
Journiac, Nathalie [Auteur]
Lille Neurosciences & Cognition (LilNCog) - U 1172
Peters, A. [Auteur]
Mars, Lennart [Auteur]
Lille Neurosciences & Cognition (LilNCog) - U 1172
ZEPHIR, Helene [Auteur]
Lille Neurosciences & Cognition (LilNCog) - U 1172

Journal title :

Frontiers in Immunology

Abbreviated title :

Front Immunol

Volume number :

13

Pages :

755900

Publication date :

2022-02-03

ISSN :

1664-3224

English keyword(s) :

B cell
repertoire
autoimmunity
experimental autoimmune encephalomyelitis (EAE)
multiple sclerosis
myelin oligodendrocyte glycoprotein (MOG)
TCR1640 transgene mouse model
demyelinating antibodies

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

The key role of B cells in the pathophysiology of multiple sclerosis (MS) is supported by the presence of oligoclonal bands in the cerebrospinal fluid, by the association of meningeal ectopic B cell follicles with ...
Show more >The key role of B cells in the pathophysiology of multiple sclerosis (MS) is supported by the presence of oligoclonal bands in the cerebrospinal fluid, by the association of meningeal ectopic B cell follicles with demyelination, axonal loss and reduction of astrocytes, as well as by the high efficacy of B lymphocyte depletion in controlling inflammatory parameters of MS. Here, we use a spontaneous model of experimental autoimmune encephalomyelitis (EAE) to study the clonality of the B cell response targeting myelin oligodendrocyte glycoprotein (MOG). In particular, 94% of SJL/j mice expressing an I-As: MOG92-106 specific transgenic T cell receptor (TCR1640) spontaneously develop a chronic paralytic EAE between the age of 60-500 days. The immune response is triggered by the microbiota in the gut-associated lymphoid tissue, while there is evidence that the maturation of the autoimmune demyelinating response might occur in the cervical lymph nodes owing to local brain drainage. Using MOG-protein-tetramers we tracked the autoantigen-specific B cells and localized their enrichment to the cervical lymph nodes and among the brain immune infiltrate. MOG-specific IgG1 antibodies were detected in the serum of diseased TCR1640 mice and proved pathogenic upon adoptive transfer into disease-prone recipients. The ontogeny of the MOG-specific humoral response preceded disease onset coherent with their contribution to EAE initiation. This humoral response was, however, not sufficient for disease induction as MOG-antibodies could be detected at the age of 69 days in a model with an average age of onset of 197 days. To assess the MOG-specific B cell repertoire we FACS-sorted MOG-tetramer binding cells and clonally expand them in vitro to sequence the paratopes of the IgG heavy chain and kappa light chains. Despite the fragility of clonally expanding MOG-tetramer binding effector B cells, our results indicate the selection of a common CDR-3 clonotype among the Igk light chains derived from both disease-free and diseased TCR1640 mice. Our study demonstrates the pre-clinical mobilization of the MOG-specific B cell response within the brain-draining cervical lymph nodes, and reiterates that MOG antibodies are a poor biomarker of disease onset and progression.Show less >

Language :

Anglais

Peer reviewed article :

Oui

Audience :

Internationale

Popular science :

Non

Collections :

• Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286
• Lille Neurosciences & Cognition (LilNCog) - U 1172
• Plateformes Lilloises en Biologie et Santé (PLBS) - UAR 2014 - US 41

Submission date :

2023-12-21T07:02:51Z
2024-02-06T19:44:15Z