Aberrant zonal recycling of germinal center B cells impairs appropriate selection in lupus.

IF 7.5 1区生物学 Q1 CELL BIOLOGY Cell reports Pub Date : 2024-11-10 DOI:10.1016/j.celrep.2024.114978

Gina M Sanchez, Eden S Hirsch, Arthur VanValkenburg, Daniel P Mayer, Komi Gbedande, Rebecca L Francis, Wenzhi Song, Olivia Q Antao, Kyleigh E Brimmer, Alexander Lemenze, Robin Stephens, W Evan Johnson, Jason S Weinstein

{"title":"Aberrant zonal recycling of germinal center B cells impairs appropriate selection in lupus.","authors":"Gina M Sanchez, Eden S Hirsch, Arthur VanValkenburg, Daniel P Mayer, Komi Gbedande, Rebecca L Francis, Wenzhi Song, Olivia Q Antao, Kyleigh E Brimmer, Alexander Lemenze, Robin Stephens, W Evan Johnson, Jason S Weinstein","doi":"10.1016/j.celrep.2024.114978","DOIUrl":null,"url":null,"abstract":"<p><p>Autoimmune diseases such as lupus are characterized by polyclonal B cell activation, leading to the production of autoantibodies. The mechanism leading to B cell dysregulation is unclear; however, the defect may lie in selection within germinal centers (GCs). GC B cells cycle between proliferation and mutation in the dark zone and selection in the light zone (LZ). Temporal assessment of GCs from mice with either persistent infection or lupus showed an accumulation of LZ B cells. Yet, only in lupus, GC B cells exhibited reduced proliferation and progressive loss of MYC and FOXO1, which regulate zonal recycling and differentiation. As lupus progressed, decreased mutational frequency and repertoire diversity were associated with reduced responsiveness to CD40 signaling, despite accumulation of plasma cells. Collectively, these findings suggest that lupus disease progression coincides with an intrinsic defect in LZ B cell signaling, altering the zonal recycling, selection, and differentiation of autoreactive B cells.</p>","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"43 11","pages":"114978"},"PeriodicalIF":7.5000,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell reports","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1016/j.celrep.2024.114978","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL BIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Autoimmune diseases such as lupus are characterized by polyclonal B cell activation, leading to the production of autoantibodies. The mechanism leading to B cell dysregulation is unclear; however, the defect may lie in selection within germinal centers (GCs). GC B cells cycle between proliferation and mutation in the dark zone and selection in the light zone (LZ). Temporal assessment of GCs from mice with either persistent infection or lupus showed an accumulation of LZ B cells. Yet, only in lupus, GC B cells exhibited reduced proliferation and progressive loss of MYC and FOXO1, which regulate zonal recycling and differentiation. As lupus progressed, decreased mutational frequency and repertoire diversity were associated with reduced responsiveness to CD40 signaling, despite accumulation of plasma cells. Collectively, these findings suggest that lupus disease progression coincides with an intrinsic defect in LZ B cell signaling, altering the zonal recycling, selection, and differentiation of autoreactive B cells.

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

红斑狼疮患者生殖中心 B 细胞的分区循环异常会影响适当的选择。

狼疮等自身免疫性疾病的特点是多克隆 B 细胞活化，从而产生自身抗体。导致 B 细胞失调的机制尚不清楚，但缺陷可能在于生殖中心（GC）内的选择。生殖中心 B 细胞在暗区的增殖和突变与亮区（LZ）的选择之间循环。对持续感染或红斑狼疮小鼠的生殖中心进行的时间评估显示，LZ B 细胞正在积累。然而，只有在狼疮患者中，GC B 细胞才会出现增殖减少、MYC 和 FOXO1 逐渐丧失的现象，而 MYC 和 FOXO1 可调控分区循环和分化。随着红斑狼疮病情的发展，突变频率和基因库多样性的降低与对CD40信号的反应性降低有关，尽管浆细胞在不断积累。总之，这些研究结果表明，狼疮疾病的进展与LZ B细胞信号传导的内在缺陷有关，它改变了自反应性B细胞的分区循环、选择和分化。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文去求助

来源期刊

Cell reports CELL BIOLOGY-

CiteScore

13.80

自引率

1.10%

发文量

1305

审稿时长

77 days

期刊介绍： Cell Reports publishes high-quality research across the life sciences and focuses on new biological insight as its primary criterion for publication. The journal offers three primary article types: Reports, which are shorter single-point articles, research articles, which are longer and provide deeper mechanistic insights, and resources, which highlight significant technical advances or major informational datasets that contribute to biological advances. Reviews covering recent literature in emerging and active fields are also accepted. The Cell Reports Portfolio includes gold open-access journals that cover life, medical, and physical sciences, and its mission is to make cutting-edge research and methodologies available to a wide readership. The journal's professional in-house editors work closely with authors, reviewers, and the scientific advisory board, which consists of current and future leaders in their respective fields. The advisory board guides the scope, content, and quality of the journal, but editorial decisions are independently made by the in-house scientific editors of Cell Reports.