14/04/2025
Key points:
Researchers from the Linterman lab at the Babraham Institute have compared the germinal centres, a hub for immune cell training, in the lung tissue with those that appear in the lymph nodes. In their study published in PNAS, they found that despite being smaller, the response formed in the tissue is capable of generating immune memory after allergen exposure. Their results show that tissue resident responses should not be overlooked when considering the immune response and suggest there may be a benefit in designing treatment delivery methods and vaccines that would induce germinal centres in the lung.
The existence of germinal centres in the lung tissue was previously described in inflammatory and autoimmune conditions, as well as in tumors where they are thought to contribute to anti-cancer immunity. The Linterman lab’s work focussed on understanding whether these lung germinal centres are functional. Typically, germinal centres form in the lymph node, where the complex pre-existing tissue architecture aids the development of the different zones needed to train and improve immune cells in response to ongoing inflammation and disease.
In contrast, the lung tissue does not provide this complex supportive environment, and so the team wanted to understand if this had an effect on the ability of the tissue-based germinal centres to support a robust immune response.
In order to generate good quality B cells, they must be trained by moving between different zones of the germinal centre, where the best B cells are selected for survival. In their study, the Linterman lab found that lung tissue germinal centres were less tightly packed but that does not prevent them from ‘training’ cells to achieve specificity to an antigen.
Dr Stephane Guillaume, who undertook this work as part of his PhD, said: “We were surprised to find that the lung can support affinity maturation within local lung-resident germinal centres to the same degree as in lymph nodes, despite their spontaneous formation. Their ability to create local populations of lung-resident memory B cells suggests it may be useful to have germinal centres form in tissues like the lung to generate protective local immunity.”
To study the germinal centre in the lung tissue, mice were exposed to allergens and then tissues were collected for analysis. Using microscopy to visualise the germinal centres, flow cytometry to determine the immune cell types present, and genetic sequencing, they were able to profile the cells from germinal centres which form in peripheral tissues and lymph nodes. To understand the effectiveness of the immune response, they evaluated the quality of B cells produced against allergens. Together, their analysis showed that although the lung response is slower than in the lymph node, the B cells produced are of high quality.
“As we learn more about germinal centres, we can hope to leverage their biology to enhance the immune response after vaccination and therefore ensure long-lasting protection from pathogens. This research indicates that designing vaccines that support tissue resident germinal centres may be a successful way to promote immunity to respiratory infections.” concluded Dr Michelle Linterman, a group leader in the Immunology programme.
Publication reference
Lung B cells in ectopic germinal centers undergo affinity maturation, PNAS, 10.1073/pnas.2416855122
Press contact
Honor Pollard, Communications Manager, honor.pollard@babraham.ac.uk
Image description: Germinal centres in the lymph node and germinal center
Affiliated authors (in author order):
Stephane Guillaume, postdoctoral researcher, Linterman lab
William Foster, postdoctoral researcher, Linterman lab
Isabel San Martín Molina, Imaging Specialist
Emily Watson, former research assistant, Linterman lab
Silvia Innocentin, research assistant, Linterman lab
Grant Kennedy, computational analytic specialist, Linterman lab
Alice Denton, group leader, Imperial College London (former postdoctoral researcher in the Linterman lab)
Michelle Linterman, associate group leader, Immunology research programme
Research funding
This research was supported by funding from the BBSRC, part of UKRI, and the European Union’s Horizon 2020 research and innovation program “ENLIGHT-TEN+” under the Marie Sklodowska-Curie grant agreement.
Animal research statement:
As a publicly funded research institute, the Babraham Institute is committed to engagement and transparency in all aspects of its research. The research presented here used tissues (mediastinal lymph node, lung) that were taken from euthanised young adult (8-16 weeks old) mice which had received genetically modified B cells and allergic immunisation to assess germinal centre formation and count immune cell proportions. These mice were used to compare the quality of the germinal centre response and B cell output between the lymph node and the lung, and to understand how the memory B cell population is locally generated. Use of a lymphocyte migration blocking compound allowed the assessment of memory B cell seeding within the lung, and single-cell sequencing of isolated B cells was used to compare clonal sharing between the lung and lymph node.
Please follow the link for further details of our animal research and our animal welfare practices. http://www.babraham.ac.uk/about-us/animal-research
About the Babraham Institute
The Babraham Institute undertakes world-class life sciences research to generate new knowledge of biological mechanisms underpinning ageing, development and the maintenance of health. Our research focuses on cellular signalling, gene regulation and the impact of epigenetic regulation at different stages of life. By determining how the body reacts to dietary and environmental stimuli and manages microbial and viral interactions, we aim to improve wellbeing and support healthier ageing. The Institute is strategically funded by the UKRI Biotechnology and Biological Sciences Research Council (BBSRC), through Institute Strategic Programme Grants and an Institute Core Capability Grant and also receives funding from other UK research councils, charitable foundations, the EU and medical charities.
About BBSRC
The Biotechnology and Biological Sciences Research Council (BBSRC) is part of UK Research and Innovation, a non-departmental public body funded by a grant-in-aid from the UK government.
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14 April 2025