MRC & Asthma UK Centre in Allergic Mechanisms of Asthma

Contact Details

Department Asthma, Allergy & Respiratory Science

5th floor, Thomas Guy House

Guy's Campus, King's College London

London

SE1 9RT

Telephone

020 7188 0613

Email

david.fear@kcl.ac.uk

Profile

To generate the enormous diversity of antibody specificities and effector functions seen in our immune systems, B cells undergo a series of DNA recombination and mutation events to assemble a functional immunoglobulin gene: The immunoglobulin variable region is assembled during V(D)J recombination and then further “fine tuned” by a process called somatic hypermutation (SHM). The effector functions of the immunoglobulin are determined by linking this variable region with one of the downstream constant region genes, producing the different isotypes - IgM, IgG, IgE and IgA, in a process known as class switch recombination (CSR). SHM and CSR are both initiated by the action of the enzyme, Activation-Induced cytidine Deaminase (AID). However, both of these processes involve the introduction of potentially damaging mutations and breaks into the DNA. Thus, the precise regulation of AID activity is crucial to ensure the normal operation of the immune system, while its miss-direction to non-immunoglobulin genes is known to lead to the development of lymphomas. To date, very little is known about what regulates CSR and SHM at a molecular level. We hypothesise that differences in the chromatin structure over the Immunoglobulin genes may target AID activity to these regions and are currently using different “omic” technologies to identify new factors that may regulate these processes and direct AID activity.

MRC & Asthma UK Centre in Allergic Mechanisms of Asthma

Last modified: 04 December 2009 11:38