Science Immunology最新文献_第5页

Mucosal tissue cues shape B cell memory through the IgA BCR 粘膜组织信号通过IgA BCR形成B细胞记忆

IF 16.4 1区医学

Science Immunology Pub Date : 2026-07-17 DOI: 10.1126/sciimmunol.adv1149

Maria Pia Holgado, Samuel Origlio, Lucas Bertoia, Myriam Moussa, Apurwa Trivedi, Frederic Fiore, Ana Zarubica, Emma Slack, Michelle A. Linterman, Michel Cogné, Claude Gregoire, Mauro Gaya

{"title":"Mucosal tissue cues shape B cell memory through the IgA BCR","authors":"Maria Pia Holgado, Samuel Origlio, Lucas Bertoia, Myriam Moussa, Apurwa Trivedi, Frederic Fiore, Ana Zarubica, Emma Slack, Michelle A. Linterman, Michel Cogné, Claude Gregoire, Mauro Gaya","doi":"10.1126/sciimmunol.adv1149","DOIUrl":"10.1126/sciimmunol.adv1149","url":null,"abstract":"<div >B cells generate plasma cells (PCs) and memory B cells (MBCs) to combat recurrent pathogens. B cell receptor (BCR) affinity dictates fate decisions in response to model antigens, but the factors regulating B cell fate during infection remain unknown. Here, we used respiratory and gastrointestinal infection models to study B cell selection across barrier tissues in mice. Memory selection was governed by tissue-specific cues: Selection in the lung was skewed toward MBCs, whereas the gut favored PC entry, even in response to the same pathogen. Divergence was linked to differential BCR isotype usage across barrier tissues rather than differential affinity maturation. In the gut, the commensal-induced TGF-β–rich milieu promoted class-switching to IgA, which skewed selection toward PCs, a process that was counteracted by the IgA cytosolic tail domain. Thus, mucosal B cell selection integrates tissue-specific cues by relying on BCR isotype usage, with implications for nasal and oral vaccine development.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"11 121","pages":""},"PeriodicalIF":16.4,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciimmunol.adv1149","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148460183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The efficacy of immunotherapy in glioma requires distal B cell responses in tumor-draining lymph nodes 免疫治疗胶质瘤的疗效需要肿瘤引流淋巴结的远端B细胞反应

IF 16.4 1区医学

Science Immunology Pub Date : 2026-07-10 DOI: 10.1126/sciimmunol.adz2494

Yumin Kim, In Kang, Byeong Hoon Kang, Won Hyung Park, Chae Won Kim, Hyun-Jin Kim, Jeongwoo La, Myoung Seung Kwon, Sang Hee Park, Seo Hyeon Im, Hyeon Cheol Kim, Keun Bon Ku, Minji Kim, Ji Eun Oh, Heung Kyu Lee

{"title":"The efficacy of immunotherapy in glioma requires distal B cell responses in tumor-draining lymph nodes","authors":"Yumin Kim, In Kang, Byeong Hoon Kang, Won Hyung Park, Chae Won Kim, Hyun-Jin Kim, Jeongwoo La, Myoung Seung Kwon, Sang Hee Park, Seo Hyeon Im, Hyeon Cheol Kim, Keun Bon Ku, Minji Kim, Ji Eun Oh, Heung Kyu Lee","doi":"10.1126/sciimmunol.adz2494","DOIUrl":"10.1126/sciimmunol.adz2494","url":null,"abstract":"<div >Humoral immunity, mediated by B cells that mature in germinal centers in lymph nodes (LNs), is essential for adaptive immune responses, but its role in antitumor immunity and responses to immunotherapy remain unclear. Here, we show that activation of B cells in tumor-draining deep cervical LNs (dcLNs) is necessary for the efficacy of CTLA-4 (cytotoxic T lymphocyte–associated protein 4) immune checkpoint blockade in glioma in vivo. Anti–CTLA-4 therapy enhanced T follicular helper cell (T<sub>FH</sub> cell) expansion in dcLNs, leading to germinal center B cell responses, immunoglobulin G (IgG) class switching, and the generation of glioma-reactive antibodies. Glioma-bearing mice lacking antibody-secreting cells did not benefit from CTLA-4 blockade. Distally secreted IgG accumulated in the tumor microenvironment and promoted glioma cell phagocytosis in vivo. These findings define a B cell–dependent mechanism underlying CTLA-4–mediated control of glioma and provide a conceptual framework for future therapeutic strategies in tumor.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"11 121","pages":""},"PeriodicalIF":16.4,"publicationDate":"2026-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148414712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Sp1 links CD46 to CD4 T cell metabolic fitness, survival, and retroviral control Sp1将CD46与CD4 T细胞代谢适应性、存活和逆转录病毒控制联系起来

IF 16.4 1区医学

Science Immunology Pub Date : 2026-07-10 DOI: 10.1126/sciimmunol.aeb5857

Parul Singh, Luopin Wang, Pavitra Ramdas, Shyaman M. Jayasundara, Gaelle Le Friec, Natalia Kunz, Prakriti Mudvari, Erin E. West, Ayden Case, Nicolas S. Merle, Jack A. Bibby, Henrik Hasle, Eli A. Boritz, Majid Kazemian, Claudia Kemper

{"title":"Sp1 links CD46 to CD4 T cell metabolic fitness, survival, and retroviral control","authors":"Parul Singh, Luopin Wang, Pavitra Ramdas, Shyaman M. Jayasundara, Gaelle Le Friec, Natalia Kunz, Prakriti Mudvari, Erin E. West, Ayden Case, Nicolas S. Merle, Jack A. Bibby, Henrik Hasle, Eli A. Boritz, Majid Kazemian, Claudia Kemper","doi":"10.1126/sciimmunol.aeb5857","DOIUrl":"10.1126/sciimmunol.aeb5857","url":null,"abstract":"<div >CD46, a human-specific complement receptor, regulates gene programs essential for T helper 1 (T<sub>H</sub>1) cell differentiation, yet how it exerts direct transcriptional control remains unclear. We show that the CD46 signaling domain cytoplasmic tail 1 (CYT-1) engages the transcription factor Sp1 in human CD4 T cells to dynamically modulate Sp1-DNA interactions. Beyond promoting T<sub>H</sub>1 cell induction, CD46-Sp1–controlled programs support naive CD4 T cell survival by maintaining nutrient transporter expression and suppressing the intrinsic caspase 9–caspase 3 apoptotic pathway. The CD46-Sp1 axis also restrains HIV transcription in infected CD4 T cells in vitro. Disruption of CYT-1–Sp1–regulated programs identifies T cells from individuals with HIV who exhibit incomplete viral suppression during antiretroviral therapy. Together, these findings define a human-specific transcriptional mechanism linking complement signaling to metabolic adaptation, apoptosis regulation, and antiviral defense, highlighting an unexpected role for CD46 in coordinating T cell homeostasis and host protection.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"11 121","pages":""},"PeriodicalIF":16.4,"publicationDate":"2026-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148415178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A breath of fresh AIR in novel CAR T cell design 在新颖的CAR - T细胞设计中呼吸新鲜空气。

IF 16.4 1区医学

Science Immunology Pub Date : 2026-07-03 DOI: 10.1126/sciimmunol.aej9802

Bin-Bin Schell, Laura Solt

引用次数: 0

Evolution and development of innate immune memory 先天免疫记忆的进化与发展

IF 24.8 1区医学

Science Immunology Pub Date : 2026-07-03 DOI: 10.1126/sciimmunol.aeb7976

Maziar Divangahi, Eva Kaufmann

引用次数: 0

ILC2s shoot 4 making 13s ILC2s拍4张，拍13张