Syndecans and glycosaminoglycans influence B-cell development and activation.

IF 6.5 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

EMBO Reports Pub Date : 2025-03-28 DOI:10.1038/s44319-025-00432-6

Craig I McKenzie, Alexandra R Dvorscek, Zhoujie Ding, Marcus J Robinson, Kristy O'Donnell, Catherine Pitt, Daniel T Ferguson, Jesse Mulder, Marco J Herold, David M Tarlinton, Isaak Quast

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引用次数: 0

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.

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Syndecans和糖胺聚糖影响b细胞的发育和活化。

Syndecans （sdc）是一种含有糖胺聚糖的细胞表面蛋白，在免疫系统中具有多种功能，在b系细胞中表达SDC1 （CD138）和SDC4。在这里，我们表明缺乏任何一种分子的干细胞产生较少的B细胞祖细胞，但在体内产生成熟的B细胞。删除浆细胞“标记物”CD138对稳态或抗原诱导的浆细胞形成没有影响。幼稚B细胞高表达SDC4，与同源抗原相遇导致短暂的CD138上调和SDC4丢失，这两种情况都由IL-4、IL-21和CD40连接进一步调节。SDC4在生发中心B细胞上下调，在大多数记忆B细胞上缺失。糖胺聚糖（如附着在sdc上的糖胺聚糖）和肝素（一种常用的治疗药物）通过限制对同源抗原的反应来调节初始B细胞的存活和激活。相反，消融SDC4导致基线和抗原诱导的b细胞活化增加。总的来说，我们的数据揭示了b细胞活化和亚群依赖性SDC表达，并表明SDC4和GAGs可以限制抗原诱导的活化，以促进b细胞的存活和扩增。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

EMBO Reports 生物-生化与分子生物学

CiteScore

11.20

自引率

1.30%

发文量

267

审稿时长

1 months

期刊介绍： EMBO Reports is a scientific journal that specializes in publishing research articles in the fields of molecular biology, cell biology, and developmental biology. The journal is known for its commitment to publishing high-quality, impactful research that provides novel physiological and functional insights. These insights are expected to be supported by robust evidence, with independent lines of inquiry validating the findings. The journal's scope includes both long and short-format papers, catering to different types of research contributions. It values studies that: Communicate major findings: Articles that report significant discoveries or advancements in the understanding of biological processes at the molecular, cellular, and developmental levels. Confirm important findings: Research that validates or supports existing knowledge in the field, reinforcing the reliability of previous studies. Refute prominent claims: Studies that challenge or disprove widely accepted ideas or hypotheses in the biosciences, contributing to the correction and evolution of scientific understanding. Present null data: Papers that report negative results or findings that do not support a particular hypothesis, which are crucial for the scientific process as they help to refine or redirect research efforts. EMBO Reports is dedicated to maintaining high standards of scientific rigor and integrity, ensuring that the research it publishes contributes meaningfully to the advancement of knowledge in the life sciences. By covering a broad spectrum of topics and encouraging the publication of both positive and negative results, the journal plays a vital role in promoting a comprehensive and balanced view of scientific inquiry.