Cosmc controls B cell homing

• Type of Material: Article
• Authors: Junwei Zeng, Harvard Medical School; Mahmoud Eljalby, Harvard Medical School; Rajindra P. Aryal, Harvard Medical School; Sylvain Lehoux, Harvard Medical School; Kathrin Stavenhagen, Harvard Medical School; Matthew R. Kudelka, Harvard Medical School; Yingchun Wang, Emory University; Jianmei Wang, Emory University; Tongzhong Ju, Emory University; Ulrich H. von Andrian, Harvard Medical School; Richard Cummings, Emory University
• Language: English
• Date: 2020-12-01
• Publisher: Nature
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) 2020.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/s41467-020-17765-6
• Title of Journal or Parent Work: Nature Communications
• Volume: 11
• Issue: 1
• Start Page: 3990
• End Page: 3990
• Grant/Funding Information: 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: Transcriptome; Venules; Polysaccharides; Mice; Mice, Inbred C57BL; Animals; Female; Immunity, Humoral; Lymph Nodes; Mice, Knockout; Glycosylation; Humans; Molecular Chaperones; Cell Movement; B-Lymphocytes; Male
• Research Categories: Biology, Microbiology; Health Sciences, Immunology; Health Sciences, Medicine and Surgery; Biology, Cell

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.