The defective gene in XLA was identified in 1993 and has allowed the development of reliable methods for the genetic counselling of XLA families. The gene is necessary for the production of a cell signalling molecule called Bruton's tyrosine kinase (Btk). However, the role of Btk in B cell development was unclear.
To investigate its role, Dr Hendriks and his colleagues first produced some mice in which the Btk gene was inactive. They have been able to prove that the absence of the gene affects B cell development at the same stage in both mice and men.
Further investigation of the function of Btk has shown that it is essential when choosing which B cells launch an attack against invading bacteria. A B cell recognises foreign bacteria through receptors on its surface. However, once a bacterial protein has become attached to the receptor a signal has to be sent to the B cell's nucleus to tell it to react. This is where Btk comes in.
Intriguingly, Btk also seems to be important in telling a B cell not to react. B cells constantly encounter so-called "autoantigens". These are proteins produced by our own bodies. When the cells of the immune system encounter autoantigens there must be some mechanism which tells them that these antigens belong to the body itself and must not be attacked. Dr Hendriks believes that in the case of B cells, Btk plays a crucial role in this process. When the "do not attack" mechanism goes wrong, autoimmune diseases such as rheumatoid arthritis and diabetes can result. Dr Hendriks hopes that his research will, in the future, also contribute to a greater understanding of these diseases, by providing knowledge on the basic mechanism of self versus non-self recognition.
In the first instance, however, Dr Hendriks aims to help boys with XLA. In their mice, Dr Hendriks and his co-workers have been able to restore the B cells to full working order by inserting the human Btk gene. This suggests that gene therapy could one day allow these children, and their families, to lead normal lives.
Notes:
1. Dr Hendriks will be speaking in the Immune Deficiency session on Wednesday 3
December 1997. The BSI 5th Annual Congress will be held at the Brighton Centre,
Brighton, UK from 2-5 December.
2. Dr Hendriks can be contacted at the Department of Cell Biology and Genetics,
Erasmus University, Rotterdam, The Netherlands. Tel: + 31 10 4088 296 Fax: + 31
10 4360 225
hendriks@ch1.fgg.eur.nl
3. There will be a press office at the meeting in operation from 9am on Tuesday
2 December. Tel. +44 1 273 724 320 / 0378 406 416 Journalists are welcome to
attend but are asked to contact Kirstie Urquhart in advance to register.
4. Before the meeting Kirstie can be contacted on +44 181 875 2402 /
kirstie@immunology.org