Helper cells aptly named in battle with invading pathogens

Aug 09, 2013 by Matt Fearer
In this mouse popliteal lymph node with germinal centers, the lymph node collagen capsule (blue) surrounds germinal centers containing follicular dendritic cells (red), antigen-specific T cells (green), and B cells (cyan). Credit: Science/AAAS

By tracking the previously unknown movements of a set of specialized cells, Whitehead Institute scientists are shedding new light on how the immune system mounts a successful defense against hostile, ever-changing invaders.

Central to the is the activity inside structures known as germinal centers (GCs), which form in the body's upon detection of a foreign virus or bacteria. Within the GCs, populations of antibody-producing B cells move through continual cycles of mutation in an effort to generate antibodies perfectly suited to bind and neutralize the harmful invader. Because the production of such high-affinity antibodies requires diversity, multiple GCs arise in a single lymph node, with each GC housing an exclusive population of B cells.

During the mutation cycles, most of the B cells in any given GC fail to achieve sufficient antibody affinity and are eliminated. A few, however, measure up, and are selected to proliferate, leave the GC, and produce the antibodies that attack the offending pathogen. This is driven by cells known as T follicular helper (Tfh) cells, which essentially cherry-pick the B cells capable of producing the most potent antibodies. Yet much of the behavior of Tfh cells has been something of a mystery. Until now.

By developing and deploying a novel cellular tagging and imaging methodology, a team of scientists led by Whitehead Fellow Gabriel Victora has discovered that, unlike their B cell counterparts, Tfh cells continually move from GC to GC within a lymph node. This surprising finding is reported in the August 9th edition of the journal Science.

Victora used to trace the Tfh cells' in the lymph nodes of living mice, noting that these cells constantly migrate between germinal centers. This activity may enhance the diversity of by introducing static B cells to a range of dynamic Tfh cells, and could help explain how the immune system copes with mutating pathogens.

"We think this could be the way our immune system can maintain a targeted immune response, even when the target is moving," says Victora, whose latest research was conducted with collaborators at the Rockefeller University in New York.

Victora believes that continued mapping of the choreography between B cells and Tfh cells has significant implications for improving vaccine development, as it suggests opportunities to influence antibody development.

"We are slowly deciphering the rules governing antibody evolution in the germinal center," he says. "This will help inform vaccine design, especially for rapidly mutating viruses like HIV. It may be that manipulating the germinal center will be necessary to produce effective vaccines."

Explore further: Malaria transmission linked to mosquitoes' sexual biology

More information: Shulman, Z. et al. T Follicular Helper Cell Dynamics in Germinal Centers, Science, August 9, 2013.

Related Stories

Ensuring the persistence of immune memory

Sep 16, 2011

Structures within the lymph nodes known as germinal centers (GCs) help the body to maintain long-term immune defense against foreign threats. The GCs essentially act as sites where antibody-producing B cells ...

Recommended for you

Malaria transmission linked to mosquitoes' sexual biology

20 hours ago

Sexual biology may be the key to uncovering why Anopheles mosquitoes are unique in their ability to transmit malaria to humans, according to researchers at Harvard T. H. Chan School of Public Health and University of Per ...

Intermediary neuron acts as synaptic cloaking device

22 hours ago

Neuroscientists believe that the connectome, a map of each and every connection between the millions of neurons in the brain, will provide a blueprint that will allow them to link brain anatomy to brain function. ...

Skeleton of cells controls cell multiplication

22 hours ago

A research team from Instituto Gulbenkian de Ciencia (IGC; Portugal), led by Florence Janody, in collaboration with Nicolas Tapon from London Research Institute (LRI; UK), discovered that the cell's skeleton ...

New study shows safer methods for stem cell culturing

Feb 25, 2015

A new study led by researchers at The Scripps Research Institute (TSRI) and the University of California (UC), San Diego School of Medicine shows that certain stem cell culture methods are associated with increased DNA mutations. ...

User comments : 0

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.