This discovery, reported in the August 22 issue of the scientific journal Immunity, provides important information on how the immune system develops, both in normal and disease states.

The laboratory of HSC senior scientist Cynthia Guidos studies the basic development of lymphocytes -- B cells and T cells -- the white blood cells that protect the body from infection. B cells develop in the bone marrow, while T cells develop in the thymus, an organ in the chest cavity.

Of particular interest has been the cellular communication pathway controlled by the Notch-1 gene, which controls T cell development, but can also cause T cell leukemia when it is mutated.

"We knew that the Notch-1 signaling pathway was required for T cell development, but how it functions was not known. Our research in a mouse model has shown that a gene called Lunatic Fringe can inhibit Notch-1 signaling. Surprisingly, Lunatic Fringe caused B cells, instead of T cells, to develop in the thymus. This shows that Notch-1 signaling is required to prevent B cells from developing in the wrong organ," said Dr. Guidos, the study's principal investigator and an associate professor of Immunology at the University of Toronto.

A number of complex cellular processes regulate the workings of the human body.

Signaling pathways act as switches to turn cellular communication on and off. Studying these switches is key to understanding cancer, a disease that results from uncontrolled cellular growth when the switches are not working properly.

"The interaction between the Notch-1 and Lunatic Fringe proteins is probably critical for determining the right balance of B cells and T cells in the immune system," added Dr. Guidos, who is also holder of a Canadian Institutes of Health Research (CIHR) Investigator Award. "It is a very fine switch -- it needs to be on for T cells to be created at all, but if it is overactive, it can cause T cell leukemia. We suspect that the Lunatic Fringe gene controls this balance."

This research was supported by the Canadian Institutes of Health Research, the National Cancer Institute of Canada with funds from the Canadian Cancer Society and The Hospital for Sick Children Foundation.

The Hospital for Sick Children is a health care, teaching and research center dedicated exclusively to children, affiliated with the University of Toronto. Its mission is to provide the best in family-centered, compassionate care, to lead in scientific and clinical advancement, and to prepare the next generation of leaders in child health.

Related website:

The Hospital for Sick Children

[Contact: Laura Greer ]

27-Aug-2001