Syndecans and glycosaminoglycans influence B-cell development and activation
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.
Authors
- Alexandra R Dvorscek (ORCID: https://orcid.org/0000-0002-8617-2422)
- Craig I. McKenzie (ORCID: https://orcid.org/0000-0001-7070-620X)
- Daniel T. Ferguson
- Zhoujie Ding (ORCID: https://orcid.org/0000-0001-8765-8814)
- Isaak Quast (ORCID: https://orcid.org/0000-0001-6517-8537)
- Marcus J Robinson (ORCID: https://orcid.org/0000-0001-5677-3078)
- Jesse Mulder
- Catherine Pitt (ORCID: https://orcid.org/0000-0001-6256-8185)
- Kristy O’Donnell (ORCID: https://orcid.org/0000-0003-1964-4685)
- David M. Tarlinton (ORCID: https://orcid.org/0000-0001-9928-686X)
- Marco J. Herold (ORCID: https://orcid.org/0000-0001-7539-7581)
Institutions
- The University of Melbourne (AU)
- Walter and Eliza Hall Institute of Medical Research (AU)
- La Trobe University (AU)
- Monash Health (AU)
- Australian Centre for HIV and Hepatitis Virology Research (AU)
- Murdoch Children's Research Institute (AU)
- Olivia Newton-John Cancer Wellness & Research Centre (AU)
- Imperial College London (GB)
- Monash University (AU)
Publication Details
- Journal
- EMBO Reports
- Published
- 2025-03-28
- DOI
- https://doi.org/10.1038/s44319-025-00432-6
- Citations
- 1
- Primary Topic
- Proteoglycans and glycosaminoglycans research
- Type
- article
- Field-Weighted Citation Impact
- 1.15
Funders
- Commonwealth Scientific and Industrial Research Organisation
- Monash University
- Australian and New Zealand Society for Immunology
- Medical Research Council
- National Health and Medical Research Council