Losing Their Grip
Authors: Davenport R. John 
Published: August 2003

To battle infections, the immune system has to recognize and grab invaders. New work suggests that with age, certain immune cells lose their hold on the molecules that identify trespassers. The study identifies for the first time a molecular defect in these cells that could weaken older immune systems.
Elderly people succumb to infections such as influenza more easily than do youngsters, and they don't develop the large numbers of specific antibodies that usually arise from repeated exposure to microbes or from vaccinations. Why age undercuts the immune system isn't clear, but researchers know that people's immune systems gradually lose the ability to generate B cells, which produce antibodies against interlopers. Antibodies bind antigens--bits of bacteria and viruses--and bring them to lymph nodes and the spleen, where follicular dendritic cells (FDCs) grab onto this so-called immune complex. FDCs then shuttle the complex to B cells, which produce a second round of antibodies with the help of T cells. The new batch of antibodies prods other immune cells to destroy the interlopers and provide resistance to future infections. Previously, Andras Szakal, an immunologist at Virginia Commonwealth University in Richmond, and colleagues found that FDCs from old animals lose their antigen-antibody-binding power. The team set out to find molecular changes that underlie the deterioration.
The team first compared FDCs from old and young mice. Animals carried similar numbers of FDCs regardless of age, but cells from old animals displayed fewer copies of the cell surface receptor that they use to pick up immune complexes. Then the researchers assessed the ability of FDCs to stimulate antibody production in a culture dish. They combined FDCs from either 12-week-old or 26-week-old mice with B cells and T cells from 12-week-olds. After exposure to a test antigen, young FDCs spurred far greater antibody output than did old FDCs. Furthermore, old B and T cells churned out antibodies as well as their younger counterparts did in the presence of young FDCs. The team is currently investigating how FDCs regulate the amount of the cell surface receptor; boosting quantities of this molecule might bolster flagging immunity. "FDCs might be a bottleneck in the aging immune system," says Szakal.
The results suggest that an age-related loss of receptors on the surface of FDCs prevents the cells from shepherding antigens to B and T cells and, as a result, suppresses antibody production. "I was taken aback," says immunologist Dennis Taub of the National Institute on Aging's branch in Baltimore, Maryland. Previous studies have shown that B and T cell function declines with age, but the new work "suggests that the FDCs themselves are responsible for the age-based loss of immune function." Not everyone is convinced. Although FDCs might play a role, the study doesn't clear B and T cells, says immunologist Robin Callard of University College London, because the cell culture studies might not re-create what happens in an intact animal. Still, the elderly might defeat infections if scientists can find a way to make their FDCs maintain a tight hold on transgressors.
--R. John Davenport

Y. Aydar, P. Balogh, J. G. Tew, A. K. Szakal, Age-related depression of FDC accessory functions and CD21 ligand-mediated repair of co-stimulation.
Eur. J. Immunol.
32
, 2817-2826 (2002).
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