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Bcl6 gene sculpts helper T cell to boost antibody production
Date:7/23/2009

HOUSTON - 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 today 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 nave 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 nave 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
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Contact: Scott Merville
smerville@mdanderson.org
713-792-0661
University of Texas M. D. Anderson Cancer Center
Source:Eurekalert

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