Syndecans and glycosaminoglycans influence B-cell development and activation

McKenzie, CI; Dvorscek, AR; Ding, Z; Robinson, MJ; O&#39;Donnell, K; Pitt, C; Ferguson, DT; Mulder, J; Herold, MJ; Tarlinton, DM; Quast, I

Author(s): McKenzie, CI; Dvorscek, AR; Ding, Z; Robinson, MJ; O'Donnell, K; Pitt, C; Ferguson, DT; Mulder, J; Herold, MJ; Tarlinton, DM; Quast, I;
Details: Publication Year 2025-05,Volume 26,Issue #9,Page 2435-2458
Journal Title: EMBO Reports
Abstract: Syndecans (SDCs) are glycosaminoglycan-containing cell surface proteins with diverse functions in the immune system with SDC1 (CD138) and SDC4 expressed in B-lineage cells. Here, we show that stem cells lacking either molecule generate fewer B-cell progenitors but give rise to mature B cells in vivo. Deletion of the plasma cell "marker" CD138 has no effect on homeostatic or antigen-induced plasma cell formation. Naive B cells express high SDC4 and encounter with cognate antigen results in transient CD138 upregulation and SDC4 loss, both further modulated by IL-4, IL-21, and CD40 ligation. SDC4 is downregulated on germinal center B cells and absent on most memory B cells. Glycosaminoglycans such as those attached to SDCs, and heparin, a commonly used therapeutic, regulate survival and activation of naive B cells by limiting responsiveness to cognate antigen. Conversely, ablation of SDC4 results in increased baseline and antigen-induced B-cell activation. Collectively, our data reveal B-cell activation- and subset-dependent SDC expression and show that SDC4 and GAGs can limit antigen-induced activation to promote B-cell survival and expansion.
Publisher: EMBO Press
Keywords: Animals; *B-Lymphocytes/immunology/cytology/metabolism; *Lymphocyte Activation; *Syndecan-1/genetics/metabolism; Mice; *Glycosaminoglycans/metabolism; *Cell Differentiation; *Syndecan-4/metabolism/genetics; Germinal Center/immunology/cytology; Interleukin-21; Interleukins/metabolism; Interleukin-4/metabolism; Mice, Inbred C57BL; Mice, Knockout; CD40 Antigens/metabolism; Plasma Cells/immunology/metabolism; B Cells; Cd138; Glycosaminoglycans; Heparin; Syndecan-4
Research Division(s): Blood Cells And Blood Cancer
PubMed ID: 40155751
Publisher's Version: https://doi.org/10.1038/s44319-025-00432-6
Open Access at Publisher's Site: https://doi.org/10.1038/s44319-025-00432-6
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2025-04-08 03:01:02

Last Modified: 2025-05-29 02:29:00