NIH scientists discover crucial control in long-lastin...(nizations. These individuals include th...),Health

Date:10/10/2008

nizations. These individuals include those with a genetic disease called X-linked lymphoproliferative disease (XLP), a rare disorder affecting approximately one in one million male children. Those affected with XLP lack SAP protein and do not have germinal centers. As a result, they have an impaired immune response to certain infections, which can prove fatal.

According to Dr. Germain, "For years, researchers tried to understand what the relationship was between the absence of germinal centers and the missing SAP protein in XLP patients by studying mouse models of the human disease, but we could not identify why the absence of SAP caused these problems."

The work by Hai Qi, M.D., Ph.D., and Jennifer Cannons, Ph.D., in the laboratories of Drs. Germain and Schwartzberg, respectively, has now solved an important piece of this puzzle. Using a special microscopy technique that allows direct visualization of immune cell actions in living mice, they observed how T and B cells and another type of white blood cell, the dendritic cell, interact dynamically within mouse lymph nodes. The research team found that T cells lacking SAP do not bind strongly to B cells carrying antigens the T cells otherwise could recognize.

"The relationship between B and T cells normally is like a pair of dancers," says Dr. Qi, the lead author. "The B cell leads and the T cell follows in a long tango that eventually goes into the germinal center."

Without SAP, however, it is as if the arms of the T-cell receptor cannot firmly grasp the antigenic arms of the B cell, and thus the tango between the two immune cells does not last. The inability of SAP-negative T cells to adhere to B cells prevents B cells from receiving crucial signals they need to become antibody-secreting cells and to generate functional germinal centers.

Another striking finding was that that SAP-negative T cells can bind to dendritic cells without any problems, although dendritic c
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Contact: Julie Wu wujuli@niaid.nih.gov 301-402-1663 NIH/National Institute of Allergy and Infectious Diseases Source:Eurekalert

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