Genetic Trigger For Disease-fighting Antibodies DiscoveredAlso:
ScienceDaily (July 17, 2009) — 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 July 16 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."
Bcl6 Gene Sculpts Helper T Cell To Boost Antibody Production
ScienceDaily (Aug. 5, 2009) — Expression of a single gene programs an immune system helper T cell that fuels rapid growth and diversification of antibodies in a cellular structure implicated in autoimmune diseases and development of B cell lymphoma, scientists at The University of Texas M. D. Anderson Cancer Center reported July 23 in Science Express, the advance online publication of the journal Science.
The gene is Bcl6, which the team found plays the crucial role in differentiating a naïve T cell into a T follicular helper cell (Tfh).
"Tfh cells were first noticed in structures called germinal centers found in the lymphoid system - in lymph nodes and the spleen," said senior author Chen Dong, Ph.D., professor in M. D. Anderson's Department of Immunology. Germinal centers are powerful machines that churn out lots of antibodies.
In the adaptive immune system, B cells present an antigen - a distinctive piece of an invading bacterium or virus - to T cells. The bound antigen converts a naïve T cell to a helper T cell that secretes cytokines which help the B cells expand and produce a large volume of antibodies to destroy an intruder.
Tfh cells are concentrated with B cells in germinal centers, where they play a helper T cell's traditional role in B cell proliferation and antibody development.
"In germinal centers, the B cells not only proliferate but they also undergo hypermutation in their immunoglobulin genes so they can produce a diverse class of antibodies," Dong said. "These mutations also allow production of antibodies with stronger affinity for their target antigens."
There are pitfalls to this process. Tfh cells and germinal centers have been implicated in antibody-mediated autoimmune diseases such as lupus and rheumatoid arthritis, Dong noted. In these diseases, the germinal centers are likely producing the wrong type of antibody at great volume.
Genetic hypermutation among B cells in germinal centers creates a hotbed of genomic instability, which gives rise to some types of B cell lymphoma, Dong said.
