Every time the human body encounters a virus, bacteria or other infectious agent, immune cells called B-lymphocytes multiply in lymph nodes and then swing into action to fight off the intruders.
When it works, it's wonderful: Germs ranging from the common cold to anthrax can be wiped out by these and other immune cells. But when this response is ineffective, serious illness can result.
That's why the discovery of a gene that's key to B-lymphocyte activation is so important, says Dr. Thomas N. Sato, Professor of Cell and Developmental Biology at Weill Medical College of Cornell University, in New York City.
"Essentially, any infectious disease or any autoimmune disease that involves B-lymphocyte activation has to go through this pathway that we've discovered, and that pathway is mediated by this gene, called KLHL6," says Dr. Sato, who joined Weill Cornell Medical College last year, and conducted much of the research leading to this discovery while at the University of Texas Southwestern, in Dallas.
The findings appear in a recent issue of Molecular and Cellular Biology.
According to Dr. Sato, "whole textbooks" have been written on the role of B-cell activity in the immune response, with myriad pathways governing this response already identified. "But the KLHL6 gene appears to be a novel component of these pathways," he says.
Here's how the response usually works: When foreign agents are detected in the body, lymphocytes first gather together in lymph nodes throughout the body and begin to proliferate, forming what experts call "germinal centers." They then spread out into the body, hunting and attacking invading germs.
"It's this growth in the germinal centers that causes your lymph nodes to swell when you've got a bad infection," Dr. Sato explains.
Previous research had uncovered a gene, and its related protein, called KLHL6, which looked like it might play a role in the B-lymphocyte process.
To find out for sure, Dr. Sato's team turned to both in vitro cell cultures and special "knock-out" mice genetically engineered to lack functional KLHL6.
"We found that in these mutant mice without a working KLHL6 gene, lymph node enlargement simply didn't occur," he said.
Just why this happens isn't entirely clear -- further studies showed that the gene wasn't essential for germinal center formation. Nevertheless, without KLHL6, B-lymphocyte activation grinds to a halt.