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Nature communications
08 10, 2020;11 (1): 3990.

Cosmc controls B cell homing.

Junwei Zeng, Mahmoud Eljalby, Rajindra P Aryal, Sylvain Lehoux, Kathrin Stavenhagen, Matthew R Kudelka, Yingchun Wang, Jianmei Wang, Tongzhong Ju, Ulrich H von Andrian, Richard D Cummings
Author Information
  1. Junwei Zeng: Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
  2. Mahmoud Eljalby: Department of Microbiology & Immunobiology, Harvard Medical School, Boston, MA, USA. ORCID
  3. Rajindra P Aryal: Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. ORCID
  4. Sylvain Lehoux: Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
  5. Kathrin Stavenhagen: Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
  6. Matthew R Kudelka: Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
  7. Yingchun Wang: Department of Biochemistry, Emory University, Atlanta, GA, USA.
  8. Jianmei Wang: Department of Biochemistry, Emory University, Atlanta, GA, USA.
  9. Tongzhong Ju: Department of Biochemistry, Emory University, Atlanta, GA, USA.
  10. Ulrich H von Andrian: Department of Microbiology & Immunobiology, Harvard Medical School, Boston, MA, USA. ORCID
  11. Richard D Cummings: Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. rcummin1@bidmc.harvard.edu. ORCID
PMID: 32778659 DOI: 10.1038/s41467-020-17765-6

Abstract

The molecular mechanisms regulating lymphocyte homing into lymph nodes are only partly understood. Here, we report that B cell-specific deletion of the X-linked gene, Cosmc, and the consequent decrease of protein O-glycosylation, induces developmental blocks of mouse B cells. After transfer into wild-type recipient, Cosmc-null B cells fail to home to lymph nodes as well as non-lymphoid organs. Enzymatic desialylation of wild-type B cells blocks their migration into lymph nodes, indicating a requirement of sialylated O-glycans for proper trafficking. Mechanistically, Cosmc-deficient B cells have normal rolling and firm arrest on high endothelium venules (HEV), thereby attributing their inefficient trafficking to alterations in the subsequent transendothelial migration step. Finally, Cosmc-null B cells have defective chemokine signaling responses. Our results thus demonstrate that Cosmc and its effects on O-glycosylation are important for controlling B cell homing.

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Grants

  1. T32 GM008169/NIGMS NIH HHS
  2. U01 CA168930/NCI NIH HHS

MeSH Term

Animals
B-Lymphocytes
Cell Movement
Female
Glycosylation
Humans
Immunity, Humoral
Lymph Nodes
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Molecular Chaperones
Polysaccharides
Transcriptome
Venules

Chemicals

Cosmc protein, mouse
Molecular Chaperones
Polysaccharides
Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

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