A cohort of highly activated CD99− CD72+ B cells promoting autoimmune progression in juvenile systemic lupus erythematosus

IF 4.8 2区 医学 Q2 IMMUNOLOGY International immunopharmacology Pub Date : 2025-03-15 DOI:10.1016/j.intimp.2025.114466
Guofeng Fang , Jing Chen , Ting Xi , Yi Liu , Yali Wu , Yini Wen , Hongxia Tang
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Abstract

CD72 inhibits the development of systemic lupus erythematosus (SLE) by suppressing TLR7-dependent B cell responses to self-nucleic acids (NAs). The absence of CD72 promotes the progression of lupus disease. Here, we find a highly activated subset of CD99 CD72+ B cells (CD72+ BCs) expressing elevated levels of TLR7 in juvenile SLE, which contributes to autoimmunity. Through multi-omics integrated analysis of single-cell RNA sequencing(scRNA-seq) data and bulk RNA sequencing (RNA-seq) data, we demonstrate that CD72+ BCs possess characteristics of both activated naïve B cells (aN) and age-associated B cells (ABCs). Concurrently, CD72+ BCs exhibit pronounced plasmablast-like features compared to other cellular subpopulations. We propose a plausible conclusion that CD72+ BCs represent a critical transitional cell population involved in the activation and subsequent plasma cell differentiation of naïve B cells and age-related B cells following exposure to self-antigens in SLE. This finding offers novel opportunities for elucidating the genesis of autoantibody-secreting cells involved in the autoimmune response processes in lupus.
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CD72 可抑制 TLR7 依赖性 B 细胞对自身核酸(NAs)的反应,从而抑制系统性红斑狼疮(SLE)的发展。CD72 的缺失会促进狼疮疾病的发展。在这里,我们发现在幼年系统性红斑狼疮中,CD99- CD72+ B细胞(CD72+ BCs)高度活化的亚群表达高水平的TLR7,这有助于自身免疫。通过对单细胞RNA测序(scRNA-seq)数据和批量RNA测序(RNA-seq)数据进行多组学综合分析,我们证明CD72+ BCs具有活化的幼稚B细胞(aN)和年龄相关B细胞(ABCs)的特征。同时,与其他细胞亚群相比,CD72+ BCs 表现出明显的浆细胞样特征。我们提出了一个可信的结论,即 CD72+ BCs 代表了一个关键的过渡性细胞群,它参与了系统性红斑狼疮患者暴露于自身抗原后的幼稚 B 细胞和年龄相关 B 细胞的活化和随后的浆细胞分化。这一发现为阐明参与狼疮自身免疫反应过程的自身抗体分泌细胞的成因提供了新的机会。
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来源期刊
CiteScore
8.40
自引率
3.60%
发文量
935
审稿时长
53 days
期刊介绍: International Immunopharmacology is the primary vehicle for the publication of original research papers pertinent to the overlapping areas of immunology, pharmacology, cytokine biology, immunotherapy, immunopathology and immunotoxicology. Review articles that encompass these subjects are also welcome. The subject material appropriate for submission includes: • Clinical studies employing immunotherapy of any type including the use of: bacterial and chemical agents; thymic hormones, interferon, lymphokines, etc., in transplantation and diseases such as cancer, immunodeficiency, chronic infection and allergic, inflammatory or autoimmune disorders. • Studies on the mechanisms of action of these agents for specific parameters of immune competence as well as the overall clinical state. • Pre-clinical animal studies and in vitro studies on mechanisms of action with immunopotentiators, immunomodulators, immunoadjuvants and other pharmacological agents active on cells participating in immune or allergic responses. • Pharmacological compounds, microbial products and toxicological agents that affect the lymphoid system, and their mechanisms of action. • Agents that activate genes or modify transcription and translation within the immune response. • Substances activated, generated, or released through immunologic or related pathways that are pharmacologically active. • Production, function and regulation of cytokines and their receptors. • Classical pharmacological studies on the effects of chemokines and bioactive factors released during immunological reactions.
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