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.
Publication types
- Research Support, N.I.H., Extramural
- Research Support, Non-U.S. Gov't
MeSH terms
- Amino Sugars / chemistry
- B-Lymphocytes / metabolism*
- Calcium Signaling
- Cell Line
- Cell Nucleus / metabolism
- Cell Proliferation
- Endocytosis
- Galectins / blood
- Galectins / metabolism*
- Germinal Center / metabolism
- Humans
- Immunologic Factors / metabolism
- Immunologic Memory
- Leukocyte Common Antigens / metabolism
- Lymphocyte Activation / immunology
- Lymphoid Tissue / metabolism
- Models, Biological
- N-Acetylhexosaminyltransferases / metabolism
- N-Acetylneuraminic Acid / metabolism
- Phosphorylation
- Polysaccharides / chemistry*
- Polysaccharides / metabolism*
- Protein Binding
- Protein Tyrosine Phosphatase, Non-Receptor Type 6 / metabolism
- Receptors, Antigen, B-Cell / metabolism*
- Sialic Acid Binding Ig-like Lectin 2 / metabolism
- Signal Transduction*
- src-Family Kinases / metabolism
Substances
- Amino Sugars
- Galectins
- Immunologic Factors
- LGALS9 protein, human
- Polysaccharides
- Receptors, Antigen, B-Cell
- Sialic Acid Binding Ig-like Lectin 2
- N-acetyllactosamine
- GCNT2 protein, human
- N-Acetylhexosaminyltransferases
- lyn protein-tyrosine kinase
- src-Family Kinases
- Leukocyte Common Antigens
- PTPN6 protein, human
- Protein Tyrosine Phosphatase, Non-Receptor Type 6
- N-Acetylneuraminic Acid