| First Author | Mortales CL | Year | 2020 |
| Journal | iScience | Volume | 23 |
| Issue | 8 | Pages | 101380 |
| PubMed ID | 32745987 | Mgi Jnum | J:338652 |
| Mgi Id | MGI:6717747 | Doi | 10.1016/j.isci.2020.101380 |
| Citation | Mortales CL, et al. (2020) N-Glycan Branching Decouples B Cell Innate and Adaptive Immunity to Control Inflammatory Demyelination. iScience 23(8):101380 |
| abstractText | 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 (TH17)/TH1 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. |
