Discovery of genetic trigger for disease-fighting antibodies

Published on July 17, 2009 at 6:36 PM · No Comments

A research team led by the La Jolla Institute for Allergy & Immunology has identified the specific gene which triggers the body to produce disease-fighting antibodies -- a seminal finding that clarifies the exact molecular steps taken by the body to mount an antibody defense against viruses and other pathogens.

The finding, published online in the journal Science, has major implications for the development of new and more effective vaccines. The La Jolla Institute's Shane Crotty, Ph.D., was the lead scientist on the team, which also included researchers from Yale University.

"The finding is enormous in terms of its long-term benefit to science and society as a whole because it illuminates a pivotal piece of the vaccine development puzzle -- that is, 'what is the molecular switch that tells the body to create antibodies?' Dr. Crotty has pinpointed the BCL6 gene and, in doing so, has answered a critical question that has long been sought by the scientific community," said Mitchell Kronenberg, Ph.D., president & scientific director of the La Jolla Institute, a nonprofit biomedical research institute. Dr. Kronenberg said this knowledge opens the door to developing ways to boost antibody production, thereby creating stronger and more effective vaccines.

Rafi Ahmed, Ph.D., director of the Emory Vaccine Center, and a professor of microbiology and immunology at the Emory University School of Medicine, called the finding an "important breakthrough."

"Dr. Crotty has defined the gene that regulates the formation of certain CD4 T cells," said Dr. Ahmed. "Those cells are very critical for antibody production, so describing what regulates the birth of those cells is clearly an important discovery."

Pamela L. Schwartzberg, M.D., Ph.D., a senior investigator in the Cell Signaling Section of the National Human Genome Research Institute, part of the National Institutes of Health, called the discovery a major step forward in the area of vaccine development. "This finding defines the master regulator (gene) that triggers an elaborate cellular interaction necessary to get effective long-term antibody responses, which are required for most successful vaccines," she said. "In making this discovery, Dr. Crotty and his fellow researchers at Yale have made a major contribution that will help provide critical insight into the processes important for successful vaccination and effective immune responses."

The finding is outlined in a paper entitled, "Bcl6 and Blimp-1 are reciprocal and antagonistic regulators of T follicular helper (TFH) cell differentiation." Yale scientist Joseph Craft, M.D., led the Yale research team, which contributed to the study.

Antibodies, Dr. Kronenberg explained, may be thought of as the body's smart bombs, which seek out infectious agents and tag them for destruction. Twenty-five human vaccines currently exist worldwide, 23 of those work by triggering the production of antibodies. "The scientific community has known for many years that antibodies were key to vaccine development and fighting infections," he continued. "But we didn't know exactly how the process worked at the cellular level and it has long been the subject of speculation, debate and intense interest."

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