{"678801":{"#nid":"678801","#data":{"type":"news","title":"Protein Handshake Holds Key to Immune Response","body":[{"value":"\u003Cdiv\u003E\u003Cdiv\u003E\u003Cdiv\u003E\u003Cdiv\u003E\u003Cdiv\u003E\u003Cp\u003EA firm handshake between proteins on immune cells is important for the body\u2019s ability to fight infection. Meanwhile, a weak grip helps explain the poor immune deficiencies caused by a rare genetic disorder.\u003C\/p\u003E\u003Cp\u003EA new study led by Georgia Tech and Emory University researcher \u003Ca href=\u0022https:\/\/research.gatech.edu\/people\/cheng-zhu\u0022\u003ECheng Zhu\u003C\/a\u003E explores the role of physical force on the immune system\u2019s ability to fight an infection. The team\u2019s discoveries could lead to new therapies that boost immune responses and improve the outcomes of patients battling a rare and devastating disease.\u003C\/p\u003E\u003Cp\u003E\u201cWith this research, we\u2019ve shown how dynamic and physical the immune system truly is,\u201d said Zhu, Regents\u0027 Professor and J. Erskine Love Jr. Chair in the \u003Ca href=\u0022https:\/\/bme.gatech.edu\/bme\/\u0022\u003EWallace H. Coulter Department of Biomedical Engineering\u003C\/a\u003E (BME).\u003C\/p\u003E\u003Cp\u003EThe work focuses on the interaction of B cells and T cells in the body\u2019s immune system via two proteins \u2014 CD40 on B cells and CD40L on T cells \u2014 in an immune deficiency disease called X-linked Hyper IgM syndrome, or X-HIgM. It\u2019s a genetic disorder affecting two out of every million newborn boys, 80% of whom die before the age of 25.\u003C\/p\u003E\u003Cp\u003EThe researchers found mechanical forces generated by these interactions create a \u201ccatch bond\u201d between the proteins. It\u2019s like a strong handshake that only gets firmer when each person tries to pull away.\u003C\/p\u003E\u003Cp\u003EWhen the bond is strong, it causes T cells to signal B cells they need to make antibodies to fight an invading pathogen. In fact, the B cells can actually switch gears, producing antibodies that are different from what they had been making.\u003C\/p\u003E\u003Cp\u003EBut people with X-HIgM have damaged CD40L proteins, resulting in weak bonds, poor signaling, and the inability to make the right antibodies.\u003C\/p\u003E\u003Cp\u003EThe team \u003Ca href=\u0022https:\/\/www.science.org\/doi\/10.1126\/sciadv.adl5815\u0022\u003Epublished their findings in \u003Cem\u003EScience Advances\u003C\/em\u003E\u003C\/a\u003E. The work emphasizes the role of mechanotransduction \u2014 the conversion of physical force into chemical activity \u2014 in the immune system.\u003C\/p\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cdiv\u003E\u003Cdiv\u003E\u003Cdiv\u003E\u003Cdiv\u003E\u003Cdiv\u003E\u003Cp\u003EZhu\u2019s fellow principal investigators in the study included Georgia Tech researcher \u003Ca href=\u0022https:\/\/bme.gatech.edu\/bme\/faculty\/Ankur-Singh\u0022\u003EAnkur Singh\u003C\/a\u003E and Juergen Wienands of the University Medical Center G\u00f6ttingen in Germany. Lead authors were BME PhD student Stefano Travaglino and former postdoc Hyun-Kyu Choi (now an assistant professor at Yonsei University in South Korea).\u003C\/p\u003E\u003Ch4\u003ETraining Camp for B Cells\u003C\/h4\u003E\u003Cp\u003EIn the body\u2019s defense system, B cells are produced in the bone marrow and migrate to a part of the lymph nodes called the germinal center.\u0026nbsp;\u003C\/p\u003E\u003Cp\u003E\u201cIt\u2019s like a training camp where B cells undergo improvement processes, including affinity maturation and antibody class switch, enhancing their ability to make effective antibodies,\u201d Travaglino said.\u0026nbsp;\u003C\/p\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cdiv\u003E\u003Cdiv\u003E\u003Cdiv\u003E\u003Cdiv\u003E\u003Cdiv\u003E\u003Cp\u003EB cells interact with and receive instructive signals from T cells to make antibodies that are most effective in coping with the pathogen invader. It\u2019s a process that relies heavily on the interaction of CD40 and CD40L.\u003C\/p\u003E\u003Cp\u003EUsing techniques like fluorescence microscopy, the researchers were able to look closely at activity in germinal centers. They used force spectroscopy tools like the biomembrane force probe which revealed that the strong, tugging handshake is suppressed by X-HIgM mutation.\u0026nbsp;\u003C\/p\u003E\u003Cp\u003EThe findings suggest that the physical environment and activity within the germinal center is just as important as the chemical signals at play between the proteins. By demonstrating how X-HIgM mutations impair catch bonds, the researchers provided a mechanistic explanation for the condition\u2019s antibody deficiencies \u2014 knowledge that could open the door to future innovations in therapeutic intervention and immunotherapy.\u003C\/p\u003E\u003Cp\u003ESingh called the team\u2019s findings \u201cnothing short of revolutionary.\u201d\u003C\/p\u003E\u003Cp\u003E\u201cThe significance of the research extends far beyond understanding X-HIgM, offering a fresh perspective on how to approach a variety of immune disorders,\u201d he said. \u201cAs this field of study evolves, the potential for advancements in immune therapies looks bright.\u201d\u003C\/p\u003E\u003Cp\u003E\u003Cstrong\u003ECITATION:\u003C\/strong\u003E Hyun-Kyu Choi, Stefano Travaglino, Matthias M\u00fcnchhalfen, Richard G\u00f6rg, Zhe Zhong, Jintian Lyu, David M. Reyes-Aguilar, J\u00fcrgen Wienands, Ankur Singh, and Cheng Zhu. \u201cMechanotransduction governs CD40 function and underlies X-linked Hyper IgM syndrome,\u201d \u003Cem\u003EScience Advances\u003C\/em\u003E. \u003Ca href=\u0022https:\/\/doi.org\/10.1126\/sciadv.adl5815\u0022\u003EDOI: 10.1126\/sciadv.adl5815\u003C\/a\u003E\u003C\/p\u003E\u003Cp\u003E\u003Cstrong\u003EFUNDING:\u003C\/strong\u003E\u0026nbsp;This research was supported by National Institutes of Health grants U01CA250040, U01CA280984, R01CA238745, and R01CA266052; The Hyper IgM Foundation AWD-004331; German Research Foundation SFB TRR 274, project A08; National Research Foundation of Korea (NRF) grant RS-2024-00337196; and the Yonsei University Research Fund 2024-22-0036. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of any funding agency.\u003C\/p\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp\u003E\u003Cbr\u003E\u003Cbr\u003E\u0026nbsp;\u003C\/p\u003E","summary":"","format":"limited_html"}],"field_subtitle":[{"value":"BME researchers explore the critical role of mechanical force in rare genetic disorder"}],"field_summary":[{"value":"\u003Cp\u003EBiomedical engineering researchers explore the role of mechanical force in the immune responses of a rare genetic disorder. Their work focuses on mechanotransduction - or how physical force influences chemical processes.\u003C\/p\u003E","format":"limited_html"}],"field_summary_sentence":[{"value":"Biomedical engineering researchers explore the role of mechanical force in the immune responses of a rare genetic disorder."}],"uid":"28153","created_gmt":"2024-12-10 16:46:31","changed_gmt":"2024-12-10 18:08:25","author":"Jerry Grillo","boilerplate_text":"","field_publication":"","field_article_url":"","location":"Atlanta, GA","dateline":{"date":"2024-12-10T00:00:00-05:00","iso_date":"2024-12-10T00:00:00-05:00","tz":"America\/New_York"},"extras":[],"hg_media":{"675803":{"id":"675803","type":"image","title":"Immune Protein interactions","body":"\u003Cdiv\u003E\u003Cdiv\u003E\u003Cdiv\u003E\u003Cdiv\u003E\u003Cp\u003EThe research team used advanced microscopy techniques to capture these images of CD40 and CD40L interactions.\u003C\/p\u003E\u003C\/div\u003E\u003Cdiv\u003E\u0026nbsp;\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp\u003E\u003Cbr\u003E\u003Cbr\u003E\u0026nbsp;\u003C\/p\u003E","created":"1733848794","gmt_created":"2024-12-10 16:39:54","changed":"1733848898","gmt_changed":"2024-12-10 16:41:38","alt":"Cd40 and Cd40L interactions","file":{"fid":"259469","name":"CD40 image.jpg","image_path":"\/sites\/default\/files\/2024\/12\/10\/CD40%20image.jpg","image_full_path":"http:\/\/hg.gatech.edu\/\/sites\/default\/files\/2024\/12\/10\/CD40%20image.jpg","mime":"image\/jpeg","size":2748962,"path_740":"http:\/\/hg.gatech.edu\/sites\/default\/files\/styles\/740xx_scale\/public\/2024\/12\/10\/CD40%20image.jpg?itok=oknRnXcT"}},"675804":{"id":"675804","type":"image","title":"Zhu and Singh","body":"\u003Cp\u003EGeorgia Tech researchers Cheng Zhu and Ankur Singh\u003C\/p\u003E","created":"1733848930","gmt_created":"2024-12-10 16:42:10","changed":"1733849016","gmt_changed":"2024-12-10 16:43:36","alt":"Cheng Zhu and Ankur Singh","file":{"fid":"259470","name":"Zhu and Singh.jpg","image_path":"\/sites\/default\/files\/2024\/12\/10\/Zhu%20and%20Singh.jpg","image_full_path":"http:\/\/hg.gatech.edu\/\/sites\/default\/files\/2024\/12\/10\/Zhu%20and%20Singh.jpg","mime":"image\/jpeg","size":601925,"path_740":"http:\/\/hg.gatech.edu\/sites\/default\/files\/styles\/740xx_scale\/public\/2024\/12\/10\/Zhu%20and%20Singh.jpg?itok=nnjPm2Dy"}}},"media_ids":["675803","675804"],"groups":[{"id":"1292","name":"Parker H. Petit Institute for Bioengineering and Bioscience (IBB)"},{"id":"1188","name":"Research Horizons"}],"categories":[{"id":"138","name":"Biotechnology, Health, Bioengineering, Genetics"},{"id":"145","name":"Engineering"},{"id":"146","name":"Life Sciences and Biology"}],"keywords":[{"id":"8963","name":"biomechanics"},{"id":"187915","name":"go-researchnews"},{"id":"187423","name":"go-bio"},{"id":"182426","name":"mechanoimmunology"},{"id":"13419","name":"Mechanotransduction"},{"id":"1895","name":"Immunology"}],"core_research_areas":[{"id":"39441","name":"Bioengineering and Bioscience"}],"news_room_topics":[{"id":"71891","name":"Health and Medicine"},{"id":"71881","name":"Science and Technology"}],"event_categories":[],"invited_audience":[],"affiliations":[],"classification":[],"areas_of_expertise":[],"news_and_recent_appearances":[],"phone":[],"contact":[{"value":"\u003Cp\u003E\u003Ca href=\u0022mailto:jerry.grillo@ibb.gatech.edu\u0022\u003EJerry Grillo\u003C\/a\u003E\u003C\/p\u003E","format":"limited_html"}],"email":["jerry.grillo@ibb.gatech.edu"],"slides":[],"orientation":[],"userdata":""}}}