B cell development and immune regulation

Our aims are to understand B cell development and diseases associated with abnormal antibody production. Inadequate or excessive immune responses lead to immunodeficiency or autoimmune and inflammatory diseases, which place a major economic and social burden on world health and the quality of human life. So, we are interested in the normal processes of immune function and how individuals vary due to inherited or acquired differences.

B cell development: modelling immunodeficiency. Much of our knowledge about immune control has come from studying rare mouse and human mutations. We are collaborating with groups in the University of Newcastle and elsewhere to study Human Mendelian mutations leading to immunodeficiency. Our latest projects involve using CRISPR/Cas9 homologous replacement in zygotes to model human disease.

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B cell selection: modelling autoimmunity and self-tolerance. We use transgenic models and other basic immunological assays to study antigen-specific B cells. This approach makes it possible for us to compare uniform populations of cells from mice with specific mutations affecting lymphocyte regulation, and track the response to foreign antigens and movement of antigen-specific cells in vivo. Current projects investigate how the immune system regulates the response to different forms of antigen and how B cells are positively selected into the naïve repertoire during ontogeny.

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Immune Regulation: developing novel therapeutics. Our final approach is to develop novel antibody-based therapeutics, which will reduce the immune or inflammatory response in human disease.  This project, which is a longstanding collaboration with Professor Simon Davis at Oxford, targets superagonists against human leukocyte inhibitory receptors.   To accelerate this work, we have developed a series of mice carrying human receptors.

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Our laboratory is part of the Medical Research Council Human Immunology Unit.   Our work is also funded by the Wellcome Trust. We are based in the Henry Wellcome Building for Molecular Physiology, which is a division of the Wellcome Trust Centre for Human Genetics.