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Author Notes:

Correspondence: Richard D. Cummings, rcummin1@bidmc.harvard.edu

Author contributions: R.D.C. and J.Z. conceived and designed the project. J.Z. performed all experiments except for glycan release and analysis, which was conducted by S.L., IgG glycopeptide analysis by K.S., chemokine receptor biochemical analysis by R.P.A., and IVM by M.E. and U.H.v.A. J.W., Y.W., and T.J. generated the floxed Cosmc mice.

J.Z., K.S., S.L., M.E., and R.P.A. analyzed and interpreted the data with the assistance of M.R.K. R.D.C., R.P.A., and J.Z. wrote the manuscript, which was edited and approved by all authors.

The authors thank Dr. Michael Reth and Dr. John Manis for providing Mb1-Cre mice. We thank the BIDMC Histology, Confocal Microscopy, and Flow cytometry Core facility staff for their assistance.

We thank Dr. Jamie Heimburg-Molinaro for help in manuscript editing and review; members of the Cummings lab and Mark B. Jones for helpful discussions. We thank Dr. Rodrigo J. Gonzalez for help in video editing.

Disclosures: The authors declare no competing interests.

Subjects:

Research Funding:

This work was supported by the HMS Center for Immune Imaging, and National Institute of Health Grant U01CA168930 to T.J. and R.D.C.

Keywords:

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

Cosmc controls B cell homing

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Journal Title:

Nature Communications

Volume:

Volume 11, Number 1

Publisher:

, Pages 3990-3990

Type of Work:

Article | Final Publisher PDF

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.

Copyright information:

© The Author(s) 2020.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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