"Germinal centers have mostly B cells with a few helper T cells to regulate them. The B cells mutate to make high-affinity antibodies and memory B cells for long-term immunity. The cell population in the germinal center structures replicates in an average of several hours, one of the fastest rates of cell replication known in mammals," Dong said.
Tracking down specialized T cell
In the Nature Medicine paper, Dong and colleagues found that a subgroup of regulatory T cells that expresses two genes, Bcl-6 and CXCR5, moves into germinal centers in both mice and humans, where they have access to B cells.
(Bcl-6 produces a protein called a transcription factor, which moves into the cell nucleus to regulate other genes. CXCR5 is a receptor protein for a signaling molecule called CXCL13.)
They also found that the Bcl-6/CXCR5 T cells aren't produced in the thymus, with other T cells, but are generated by regulatory T cell precursor cells that express Foxp3, another transcription factor.
Knocking out the regulatory T cells that express all three proteins in mice resulted in increased germinal center production of antibodies. They named this key T cell the T follicular regulatory cell, or Tfr.
In a 2009 paper in the journal Science, the researchers found that nave T cells that expressed Bcl-6 and CXCR5 also gathered in the B cell zone of germinal centers. Expression of Bcl6 converted the T cell into a T follicular helper (Tfh) cell that launches antibody production in the germinal centers.
With Tfr turning germinal centers off and Tfh turning them on, we could potentially regulate antibody production, Dong noted. Increasing Tfr production could be a new approach to treatin
|Contact: Scott Merville|
University of Texas M. D. Anderson Cancer Center