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Explore a selection of research case studies from the past five years.

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Researchers at the Crick are tackling the big questions about human health and disease, and new findings are published every week.

Our faculty have picked some of the most significant papers published by Crick scientists, all of which are freely available thanks to our open science policy.

B cell selection process

B cell selection process outlined

To mount a robust immune response, immune cells called IgG1 B cells must be selected within the germinal centres of lymphoid organs to produce high affinity antibodies against pathogens. Despite the importance of this process, its mechanism remains largely elusive. By investigating the role of genes in germinal centre B cells, researchers at the Crick revealed that a protein called MIZ1 was critical for the selection of IgG1 B cells and production of high-affinity antibodies. Specifically, MIZ1, a protein known for its role in gene regulation, was identified as a key player in driving the expression of TMBIM4, which ultimately prevented IgG1 B cell death due to excessive calcium signalling, ensuring IgG1 B cell survival during the critical selection process. These findings underscore the significance of MIZ1 and TMBIM4 in shaping the immune response during infection and vaccination.

Regulation of BCR-mediated Ca2+ mobilization by MIZ1-TMBIM4 safeguards IgG1+ GC B cell-positive selection

Published in Science Immunology

Published

Follicular dendritic networks in an immunised lymph node

Molecular mechanism of antigen retention in immune response unveiled

Research led by UCL and the Francis Crick Institute has identified the biological mechanisms by which antigens are captured, stored and replaced in lymph nodes after vaccination and how they regulate B cell and antibody responses.

The findings, published in Nature Immunology, provide valuable insight into human immune responses and point the way to understanding how the immune system could become better equipped to recognise and eliminate specific pathogens - leading to more efficient and targeted immune responses and vaccine design.

Their findings showed that the structure and arrangement of the follicular dendritic network - a specialised network of cells within the lymph node - made a difference in how antigens were captured and used. The team identified that only the cells in the centre of the network functioned as an antigen reservoir, whereas those on the periphery did not, and the molecular mechanisms underpinning this. This discovery has implications for the potential development of more efficient vaccines.

Long-term retention of antigens in germinal centers is controlled by the spatial organization of the follicular dendritic cell network

Published in Nature Immunology

Published

Image showing the structure of IgM and its receptor on lymphocytes.

3D structure of immunoglobin M and its receptor revealed

Antibodies are proteins that protect the body by binding to protein targets (called antigens) on bacteria and viruses. Immunoglobin M is the class of antibody that is produced first during an infection. Complexes of antibodies and antigens can be recognised by protein receptors located on immune cells called lymphocytes, which leads to further immune responses. This research used cryo-electron microscopy to determine the three-dimensional structure of IgM in complex with an IgM-specific receptor present on lymphocytes called B-cells. IgM is involved in many different immune responses, and the structure can help us to understand immune response to disease.

This research was led by Qu Chen and was a collaboration between the Structural Biology Science and Technology Platform, the Tolar Laboratory and the Rosenthal Laboratory.

Structural basis for Fc receptor recognition of immunoglobulin M

Published in Nature Structural and Molecular Biology

Published

A therapeutic target for two diseases

Research from the Hill lab has identified the underlying molecular mechanism for two diseases that share a common causal mutation and currently have no effective treatments. The team used optogenetics and live-imaging approaches to show the link between genetic mutation and disrupted signalling that causes these diseases.

Pathogenic ACVR1R206H activation by Activin A-induced receptor clustering and autophosphorylation

Published in The EMBO Journal

Published

Germinal center B cells recognize antigen through a specialized immune synapse architecture

Using new high-throughput imaging designed for rare cell subsets, we revealed that germinal centre B cells form uniquely patterned immune synapses to bind antigens. The separation of antigen into small clusters, along with specific cytoskeletal organisation results in enhanced mechanical forces transferred onto the B cell receptor-antigen bonds, increasing the mechanical affinity-discrimination power of germinal centre B cells compared to other B cell subsets. The work implicated germinal centre B cell mechanics in selection of high-affinity B cell clones in antibody responses and introduced novel DNA nanosensors for measuring cellular forces.

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Published in Nature Immunology

Published

B cell antigen extraction is regulated by physical properties of antigen-presenting cells

We demonstrated that mechanical forces and not enzymatic liberation are the physiological mechanism for acquisition of antigens by B cells from live presenting cells. Using DNA-based nanosensors we showed that B cell affinity discrimination is regulated by physical properties of the antigen-presenting cells and identified follicular dendritic cells as a stiff antigen presenting subset that promotes B cell affinity discrimination in germinal centres.

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Published in Journal of Cell Biology

Published

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Research case studies 

Explore a selection of recent case studies that spotlight particular areas of research at the Crick.