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Blizard Paper of the Year reveals groundbreaking insights into lifelong immunity

Research into immune memory in humans creates roadmap of germinal centres that could be the key to effective vaccines

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A child being vaccinated

A child being vaccined

A study led by Sir Henry Wellcome Postdoctoral Fellow, Dr Hamish King, involving researchers from the Blizard Institute, Barts Cancer Institute, Wellcome Sanger Institute and The Royal London Hospital, gives new understanding of the germinal centre response to infection and its role in immune memory. Using innovative single cell genomics on cells found in human tonsils, researchers were able to measure the genes expressed by tens of thousands of individual cells and the genetic sequence that produces their antibody.

Published in Science Immunology in February this year, the study was one of the first and most detailed uses of single cell genomics to perform an unbiased annotation and dissection of different B cell populations within active germinal centres. As such, it was voted Blizard Institute Paper of the Year 2021 during the annual Blizard Symposium held at the Blizard Institute on Wednesday 24 November.

New insights into the behaviour of B cells within the germinal centre

We know that germinal centres play a vital role in the body’s immune system. Formed in the lymph nodes, spleen and tonsils, they’re where immune cells assemble and interact during an immune response. B cells that enter a germinal centre are key to creating “immune memory” that can protect the body from future infection.

B cells make antibodies in response to infections or vaccinations, which bind to pathogens and destroy them or trigger other immune cells into action. B cells that enter germinal centres can evolve stronger antibodies and become long-lived cells that protect us from future infection by that same pathogen.

While the importance of the germinal centre to immune memory has been generally understood, their complexity has long made it difficult to fully understand the behaviour of B cells once inside the centre.

The cutting-edge technology identified unexpected and rare types of B cells that are otherwise undetected by other technologies available. With their findings, the research team reconstructed the entire germinal centre response, which showed us exactly how different B cells evolve from the moment they detect a pathogen through to immune memory formation.

Implications for disease and vaccine development

Lead author Dr Hamish King said: “Because B cells need germinal centres to develop immune memory, the more we can discover about these different factors, the better our understanding of our susceptibility to different diseases. By mapping the different types and function of B cells in high resolution, we are learning more about this essential process in normal tissues. Additionally, our paper and datasets are providing other researchers who study B cell-related diseases (like lymphoma, multiple sclerosis, rheumatoid arthritis, and many others) with a reference roadmap of how normal B cells look to help them understand what can go wrong in disease.

“Understanding precisely how germinal centres work is key to designing effective vaccines that generate lifelong immunity. In the future, combining different technologies such as those we used in our study with other methods would allow us to directly compare immune responses to vaccines against many infectious agents, like the coronavirus SARS-CoV-2, and understand immune memory, more generally."

This article was adapted from an article written for The Conversation by authors Dr Hamish King and Dr Louisa James.

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