Galectin-9 suppresses B cell receptor signaling and is regulated by I-branching of N-glycans

N. Giovannone, J. Liang, A. Antonopoulos, J. Geddes Sweeney, S. L. King, S. M. Pochebit, N. Bhattacharyya, G. S. Lee, A. Dell, H. R. Widlund, S. M. Haslam () and C. J. Dimitroff ()
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N. Giovannone: Brigham and Women’s Hospital
J. Liang: Brigham and Women’s Hospital
A. Antonopoulos: Imperial College London
J. Geddes Sweeney: Brigham and Women’s Hospital
S. L. King: Brigham and Women’s Hospital
S. M. Pochebit: Harvard Medical School
N. Bhattacharyya: Division of Otolaryngology, Brigham and Women’s Hospital
G. S. Lee: Harvard Medical School
A. Dell: Imperial College London
H. R. Widlund: Brigham and Women’s Hospital
S. M. Haslam: Imperial College London
C. J. Dimitroff: Brigham and Women’s Hospital

Nature Communications, 2018, vol. 9, issue 1, 1-17

Abstract: Abstract Leukocytes are coated with a layer of heterogeneous carbohydrates (glycans) that modulate immune function, in part by governing specific interactions with glycan-binding proteins (lectins). Although nearly all membrane proteins bear glycans, the identity and function of most of these sugars on leukocytes remain unexplored. Here, we characterize the N-glycan repertoire (N-glycome) of human tonsillar B cells. We observe that naive and memory B cells express an N-glycan repertoire conferring strong binding to the immunoregulatory lectin galectin-9 (Gal-9). Germinal center B cells, by contrast, show sharply diminished binding to Gal-9 due to upregulation of I-branched N-glycans, catalyzed by the β1,6-N-acetylglucosaminyltransferase GCNT2. Functionally, we find that Gal-9 is autologously produced by naive B cells, binds CD45, suppresses calcium signaling via a Lyn-CD22-SHP-1 dependent mechanism, and blunts B cell activation. Thus, our findings suggest Gal-9 intrinsically regulates B cell activation and may differentially modulate BCR signaling at steady state and within germinal centers.

Date: 2018
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DOI: 10.1038/s41467-018-05770-9

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