Gene Found to Stimulate Infection-Fighting Cells

When the immune system comes across a virus, bacteria, or other infectious agents, cells called B-lymphocytes multiply in lymph nodes and then jump into action to fight off the invaders. When it works, it is an incredible process. Germs ranging from the common cold to anthrax can be destroyed by these and other immune cells. But when this response is ineffective, serious illness can result.

That is why a finding of a gene that is vital to B-lymphocyte activation is so significant, according to Dr. Thomas N. Sato, professor of cell and developmental biology at Weill Medical College of Cornell University (New York, NY, USA). "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,” remarked Dr. Sato, who performed much of the research leading to this discovery while at the University of Texas Southwestern (Dallas, TX, USA).

The findings appear in the April 2006 issue of the journal 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 controlling this response already identified. "But the KLHL6 gene appears to be a novel component of these pathways,” he stated.

The response typically functions like this: when foreign organisms are detected in the body, lymphocytes first congregate in lymph nodes throughout the body and start to proliferate, forming what scientists call "germinal centers.” They then spread out into the body, searching 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 explained.

Earlier studies had found a gene and its related protein, called KLHL6, which looked like it might play a role in the B-lymphocyte process. To verify this, Dr. Sato's group looked at both in vitro cell cultures and special "knock-out” mice genetically modified 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 is not completely clear--additional research showed that the gene was not essential for germinal center formation. Nevertheless, without KLHL6, B-lymphocyte activation halts.

The next step, according to the researchers, is to find an agent that might stimulate KLHL6 function. "Ideally, in the presence of infection, you want proper B-lymphocyte activity or even enhanced activity,” Dr. Sato explained. "So we plan on screening small molecules that might help with this pathway.”

Whereas the potential for KLHL6-enhancing agents is not yet known, they might someday prove beneficial against a number of viral or bacterial illnesses, including HIV/AIDS. "Further stimulating our bodies' ability to either up-regulate the expression of KLHL6 or other components of that pathway might make us less susceptible to infections,” Dr. Sato stated, "not only in helping us recover better from these types of illnesses, but in making us more resistant to infection in the first place.”



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Weill Medical College of Cornell University