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Profile: Dr Ken Smith

Principal investigators


Title: University Lecturer

Contact: Tel: 01223 762 645; Secretary: Denise Schofield Tel: 01223 762 812 E-mail: kgcs2@cam.ac.uk

Home department: Medicine

Negative regulation of the immune response in health and disease
The immune response is controlled by cell surface molecules which act as negative regulators or brakes, preventing or turning off cellular activation. Knockout mice with defects in these negative regulatory systems develop immune hyperactivity and autoimmunity. Our group aims to understand how these molecules regulate the normal immune response, and how defects in their action cause autoimmune disease.

  1. Negative regulation and the normal immune response.
  2. We have shown that interleukin-4 reduces expression of negative regulators on B cells, suggesting that IL-4 may enhance the B cell immune response by releasing the B cell from inhibition, rather than by directly activating it. We are investigating the functional consequences of this reduced expression, and whether IL-4 has a similar effect in other cell types. In addition, we are studying the role played by the inhibitory Fc receptor FcγRII in feedback control of the B cell response and on affinity maturation.

  3. Defective negative regulation and autoimmune disease.
  4. Systemic lupus erythematosus (SLE) is an autoimmune disease arising from the combined effects of multiple susceptibility genes. Fcg RIIb inhibits activation of cells including B cells and macrophages. We have identified reduced expression and function of Fcg RII in all major SLE-prone mouse strains. The resulting immune hyperactivity is likely to make a fundamental contribution to disease. We are examining how reduced Fcg RII causes autoimmunity, and how such genetic "defects" have evolved in the wild mouse population.

  5. The B cell immune response and viral immune modulators.

We are analysing how murine γ-herpesvirus 68 (related to human Epstein Barr virus) influences B cell gene expression using microarray technology and viruses deficient in potential immmunomodulatory genes [with Dr Paul Lyons (profile), DIL, and Dr Stacey Efstathiou, Virology].This should provide insight not only into mechanisms of viral pathogenesis, but may also identify novel B cell signalling pathways.


Group members:

Key publications


Last updated: 8 May 2003

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