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N-Glycan Branching Decouples B Cell Innate and Adaptive Immunity to Control Inflammatory Demyelination

B cell depletion potently reduces episodes of inflammatory demyelination in multiple sclerosis (MS), predominantly through loss of innate rather than adaptive immunity. However, molecular mechanisms controlling innate versus adaptive B cell function are poorly understood. N-glycan branching, via int...

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Detalles Bibliográficos
Autores principales: Mortales, Christie-Lynn, Lee, Sung-Uk, Manousadjian, Armen, Hayama, Ken L., Demetriou, Michael
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7398982/
https://www.ncbi.nlm.nih.gov/pubmed/32745987
http://dx.doi.org/10.1016/j.isci.2020.101380
Descripción
Sumario:B cell depletion potently reduces episodes of inflammatory demyelination in multiple sclerosis (MS), predominantly through loss of innate rather than adaptive immunity. However, molecular mechanisms controlling innate versus adaptive B cell function are poorly understood. N-glycan branching, via interactions with galectins, controls endocytosis and signaling of cell surface receptors to control cell function. Here we report that N-glycan branching in B cells dose dependently reduces pro-inflammatory innate responses by titrating decreases in Toll-like receptor-4 (TLR4) and TLR2 surface expression via endocytosis. In contrast, a minimal level of N-glycan branching maximizes surface retention of the B cell receptor (BCR) and the CD19 co-receptor to promote adaptive immunity. Branched N-glycans inhibit antigen presentation by B cells to reduce T helper cell-17 (T(H)17)/T(H)1 differentiation and inflammatory demyelination in mice. Thus, N-glycan branching negatively regulates B cell innate function while promoting/maintaining adaptive immunity via BCR, providing an attractive therapeutic target for MS.