Dr. Crotty said it has been well established that antibody production is a multi-step process that involves interactions between several cellular players, key among them CD4 "helper" T cells, which are disease-fighting white blood cells that tell other cells to produce antibodies in response to infections. "There were different flavors of these CD4 helper T cells and, for many years, we, in the scientific community, thought that one of the four varieties of CD4 helper type 2 cells (known as TH-2 cells) triggered the antibody process. But about 10 years ago, scientists realized this was incorrect and that there must exist a fifth variety of CD4 helper T cell that initiated antibody production. It was named TFH."

Dr. Crotty's team set out to understand the inner workings of the TFH pathway. "We discovered that the BCL6 gene was like an on and off switch, or master regulator, in this process. In a series of experiments, we showed that if you turn on this gene, you get more CD4 T helper cells (the TFH type) and it's those cells that are telling the B cells to produce antibodies," he said.

Dr. Crotty's group also tested the finding by using a cellular mechanism to turn off the BCL6 gene. Turning off the gene stopped the production of the TFH cells. "Without this genetic trigger, no TFH cells were produced and consequently no antibodies." The researchers also found that the more TFH cells produced, the greater the antibody response.

Yale researchers, who were collaborators on the study, also tested and proved the finding by deleting the BCL6 gene. "Beautifully, they got the same results “ antibody production ceased," said Dr. Crotty.

The finding also may have implications for rheumatoid arthritis and some other autoimmune diseases. "Some autoimmune diseases are triggered by antibody-induced inflammation," said Dr. Crotty. "The ability to turn antibody production off may also offer therapeutic opportunities for these people."

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