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Syndecans and glycosaminoglycans influence B-cell development and activation
Craig I McKenzie1,2, Alexandra R Dvorscek3,4, Zhoujie Ding3
1Department of Immunology, Monash University, Melbourne, VIC, 3004, Australia. craig.mckenzie@monash.edu.
EMBO Reports
|March 29, 2025
Summary
Syndecans (SDC) are cell surface proteins crucial for immune cell function. This study reveals SDC4 and glycosaminoglycans limit B-cell activation, promoting survival and expansion.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Syndecans (SDCs) are cell surface proteoglycans involved in immune system regulation.
- SDC1 (CD138) and SDC4 are expressed in B-lineage cells, playing roles in their development and function.
Purpose of the Study:
- To investigate the role of SDC4 and SDC1 in B-cell development, activation, and subset differentiation.
- To elucidate how SDC expression changes during B-cell activation and how SDCs influence B-cell responses to antigen.
Main Methods:
- Analysis of B-cell development and function in mice lacking SDC1 or SDC4.
- Flow cytometry to assess cell surface expression of SDCs on different B-cell subsets.
- Investigation of the impact of cytokines (IL-4, IL-21) and CD40 ligation on SDC expression.
Main Results:
- Stem cells lacking SDC1 or SDC4 showed altered B-cell progenitor generation but produced mature B cells.
- SDC4 is highly expressed on naive B cells and downregulated on germinal center and memory B cells.
- Loss of SDC4 led to increased baseline and antigen-induced B-cell activation.
- Glycosaminoglycans (GAGs), including those on SDCs, limit naive B-cell responsiveness to antigen.
Conclusions:
- SDC expression is dynamically regulated during B-cell activation and differentiation.
- SDC4 and associated GAGs act as negative regulators of B-cell activation, promoting survival and expansion.
- Targeting SDCs or GAGs could offer new strategies for modulating B-cell immune responses.
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