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Unmasking of CD22 on germinal center B-cells occurs by alternative mechanisms in mouse and man

  • Author(s) / Creator(s)
  • CD22 is an inhibitory B-cell co-receptor whose function is modulated by sialic acid (Sia)-bearing glycan ligands. Glycan remodeling in the germinal center (GC) alters CD22 ligands, with as yet no ascribed biological consequence. Here, we show in both mice and humans that loss of high affinity ligands on GC B-cells unmasks the binding site of CD22 relative to naive and memory B-cells, promoting recognition of trans ligands. The conserved modulation of CD22 ligands on GC B-cells is striking because high affinity glycan ligands of CD22 are species-specific. In both species, the high affinity ligand is based on the sequence Siaα2–6Galβ1–4GlcNAc, which terminates N-glycans. The human ligand has N-acetylneuraminic acid (Neu5Ac) as the sialic acid, and the high affinity ligand on naive B-cells contains 6-O-sulfate on the GlcNAc. On human GC B-cells, this sulfate modification is lost, giving rise to lower affinity CD22 ligands. Ligands of CD22 on naive murine B-cells do not contain the 6-O-sulfate modification. Instead, the high affinity ligand for mouse CD22 has N-glycolylneuraminic acid (Neu5Gc) as the sialic acid, which is replaced on GC B-cells with Neu5Ac. Human naive and memory B-cells express sulfated glycans as high affinity CD22 ligands, which are lost on GC B-cells. In mice, Neu5Gc-containing glycans serve as high affinity CD22 ligands that are replaced by Neu5Ac-containing glycans on GC B-cells. Our results demonstrate that loss of high affinity CD22 ligands on GC B-cells occurs in both mice and humans through alternative mechanisms, unmasking CD22 relative to naive and memory B-cells.

  • Date created
    2015
  • Subjects / Keywords
  • Type of Item
    Article (Published)
  • DOI
    https://doi.org/10.7939/R3BG2HR13
  • License
    © 2015 Matthew S. Macauley et al. This version of this article is open access and can be downloaded and shared. The original author(s) and source must be cited.
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  • Citation for previous publication
    • Macauley, Matthew S., Kawasaki, Norihito, Peng, Wenjie, Wang, Shui-Hua, He, Yuan, Arlian, Britni M., McBride, Ryan, Kannagi, Reiji, Khoo, Kay-Hooi, & Paulson, James C. (2015). Unmasking of CD22 on germinal center B-cells occurs by alternative mechanisms in mouse and man. Journal of Biological Chemistry, 290(50), 30066-30077. http://doi.org/10.1074/jbc.M115.691337
  • Link to related item
    http://doi.org/10.1074/jbc.M115.691337