Featured Research

from universities, journals, and other organizations

Crucial Control In Long-lasting Immunity Discovered

Date:
October 11, 2008
Source:
NIH/National Institute of Allergy and Infectious Diseases
Summary:
Scientists have identified a protein that links two key types of white blood cells, T and B cells, letting them interact in a way that is crucial to establishing long-lasting immunity after an infection. Their finding may also explain why some individuals who have a genetic defect that prevents them from making this protein suffer from lethal infections with a common virus that otherwise is rarely fatal, while others have problems with B-cell lymphomas.

A pair of normal T cells (blue) and B cells (red) depicted at the right of this view stay together for extended periods of time, while SAP-deficient T cells (green) do not stay with the B cells (red). The SAP-deficient T cells are unable to send signals to cause the pair to differentiate into germinal centers which provide long-lasting antibody immunity.
Credit: Image courtesy of NIH/National Institute of Allergy and Infectious Diseases

National Institutes of Health (NIH) scientists have identified a protein that plays matchmaker between two key types of white blood cells, T and B cells, enabling them to interact in a way that is crucial to establishing long-lasting immunity after an infection.

Their finding may also explain why some individuals who have a genetic defect that prevents them from making this protein—called SAP—suffer from lethal infections with a common virus that otherwise is rarely fatal (Epstein-Barr virus), while others with this genetic defect have problems with B-cell lymphomas.

The new study was a collaboration between the laboratories of NIH scientists Ronald Germain, M.D., Ph.D., at the National Institute of Allergy and Infectious Diseases (NIAID), and Pamela Schwartzberg, M.D., Ph.D., at the National Human Genome Research Institute (NHGRI). Their findings appear in the Oct. 9 issue of Nature.

When a B cell encounters a virus or other foreign agent, the B cell engulfs the virus and parts of it, called antigens, become displayed on the surface of the B cell. These antigens signal to T cells, which have specialized receptors that can bind to antigens on the B cells. Thus coupled, the T cells deliver signals that help B cells multiply and produce antibodies that will eventually destroy the offending virus. A critical tissue structure that facilitates these events is the germinal center, which normally forms after an infection within the lymph nodes, organs in which immune cells gather to carry out their functions.

"Understanding how B and T cells interact in the lymph nodes is crucial, because the germinal centers are the sites where long-lasting immunity begins," says NIAID Director Anthony S. Fauci, M.D. "If we can unravel how the body naturally builds defenses against repeat infections, it will aid us in developing more effective vaccines."

In some individuals, B cells do not make antibodies in response to infections and immunizations. 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 cells have antigenic arms similar to those of B cells. Dr. Cannons explains, "Some cell receptors act like Velcro, allowing two different cells to stick together. We think that different cells use different receptor signals to stick together. A signal that does not affect the sticking between two cell types may well prevent another two cell types from interacting."

These findings not only help explain the basis for the immunodeficiency disease known as XLP, but also provide important new insights into the exquisitely specific communications between different types of immune cells.

According to Dr. Schwartzberg, "This work provides a great example of the power of combining mouse models of human diseases with live imaging microscopy to uncover secrets of the immune system and help discover new ways to combat disease."

"This work nicely demonstrates both the value of interdisciplinary collaboration and that exploring relatively rare genetic diseases can offer important insights into biological processes that are important to the health of all of us," says Alan E. Guttmacher, M.D., acting director, NHGRI.


Story Source:

The above story is based on materials provided by NIH/National Institute of Allergy and Infectious Diseases. Note: Materials may be edited for content and length.


Journal Reference:

  1. Qi et al. SAP-controlled T–B cell interactions underlie germinal centre formation. Nature, 2008; 455 (7214): 764 DOI: 10.1038/nature07345

Cite This Page:

NIH/National Institute of Allergy and Infectious Diseases. "Crucial Control In Long-lasting Immunity Discovered." ScienceDaily. ScienceDaily, 11 October 2008. <www.sciencedaily.com/releases/2008/10/081010135031.htm>.
NIH/National Institute of Allergy and Infectious Diseases. (2008, October 11). Crucial Control In Long-lasting Immunity Discovered. ScienceDaily. Retrieved September 17, 2014 from www.sciencedaily.com/releases/2008/10/081010135031.htm
NIH/National Institute of Allergy and Infectious Diseases. "Crucial Control In Long-lasting Immunity Discovered." ScienceDaily. www.sciencedaily.com/releases/2008/10/081010135031.htm (accessed September 17, 2014).

Share This



More Health & Medicine News

Wednesday, September 17, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

President To Send 3,000 Military Personnel To Fight Ebola

President To Send 3,000 Military Personnel To Fight Ebola

Newsy (Sep. 16, 2014) President Obama is expected to send 3,000 troops to West Africa as part of the effort to contain Ebola's spread. Video provided by Newsy
Powered by NewsLook.com
Obama Orders Military Response to Ebola

Obama Orders Military Response to Ebola

AP (Sep. 16, 2014) Calling the Ebola outbreak in West Africa a potential threat to global security, President Barack Obama is ordering 3,000 U.S. military personnel to the stricken region amid worries that the outbreak is spiraling out of control. (Sept. 16) Video provided by AP
Powered by NewsLook.com
UN: 20,000 Could Be Infected With Ebola by Year End

UN: 20,000 Could Be Infected With Ebola by Year End

AFP (Sep. 16, 2014) Nearly $1.0 billion dollars is needed to fight the Ebola outbreak raging in west Africa, the United Nations say, warning that 20,000 could be infected by year end. Duration: 00:40 Video provided by AFP
Powered by NewsLook.com
Obama: Ebola Outbreak Threat to Global Security

Obama: Ebola Outbreak Threat to Global Security

AP (Sep. 16, 2014) President Obama is ordering U.S. military personnel to West Africa to deal with the Ebola outbreak, which is he calls a potential threat to global security. (Sept. 16) Video provided by AP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

    Technology News



    Save/Print:
    Share:

    Free Subscriptions


    Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

    Get Social & Mobile


    Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

    Have Feedback?


    Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
    Mobile: iPhone Android Web
    Follow: Facebook Twitter Google+
    Subscribe: RSS Feeds Email Newsletters
    Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins