Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Scientists Show How Memory B Cells Stay 'In Class' to Fight Different Infections

08.05.2012
Scientists at The Scripps Research Institute have made an important discovery about the internal programming of B cells, the immune cells that make antibodies against infections.
The finding opens the way for the development of vaccines that can work more efficiently and hints at therapies for conditions in which B cells cause harm—such as the autoimmune disease lupus erythymatosus, severe allergies, and B-cell lymphomas.

The discovery reveals that B cells produce special proteins to maintain themselves in a particular functional “class,” even as they lie dormant in the memory-cell state, awaiting a new infection. The class of a B cell determines how its antibodies marshal other components of immunity, and thus how well they can remove a certain type of threat, say bacteria on the skin versus intestinal parasites.
“This is a real breakthrough, in the sense that we now have a much better understanding of how B cell class is regulated, and how we might target that regulatory process in vaccine and drug design,” said Michael McHeyzer-Williams, a Scripps Research professor who was the principal investigator for the study, published in Nature Immunology’s advance online edition on May 6, 2012.

Specialized Infection Fighters

Young, “naïve” B cells begin their careers as infection fighters when they are exposed, in the right way, to pieces of an invading microbe that happen to match their main receptor (the B cell receptor, or BCR). Some then become plasma B cells, and slowly ramp up the active production of antibodies. Others instead become memory B cells, which can lie in wait for years, primed to respond very rapidly and nip in the bud any reinfection.
Either way, as B cells move out of the naïve state, helper T cells secrete chemical signals that typically force the B cells into particular classes. IgG-class B cells are the most common in humans, and are broadly effective against viruses and bacteria. IgA-class B cells are predominantly found on mucosal surfaces such as in the throat and intestines. IgE-class cells and their antibodies protect against intestinal worms and other parasites. Some B cells stay in the default IgM class. The class of a B cell is marked by the type of “stem” it has on its Y-shaped antibodies; this stem, or effector, can mobilize other elements of the immune system, such as inflammatory chemicals, when the antibody binds to an invader.

It had been long assumed that the switching of a B cell to a particular class is the result of a one-time signaling event. “The idea was that the signals that produce this switch don’t persist in B memory cells, for example,” said Nathaniel Wang, a graduate student in the Scripps Research Kellogg School of Science and Technology working in the McHeyzer-Williams laboratory who was first author of the new study.

Testing Assumptions

In the study, Wang, McHeyzer-Williams, and their colleagues tried to determine whether that assumption is true. They knew, for example, that when T cells cause naïve B cells to switch to the IgG2a class, a potent antiviral class, they do so by inducing the production in B cells of a particular protein called T-bet. To clarify T-bet’s role, the researchers engineered transgenic mice whose B cells lack the protein.

Without T-bet, they found, the mouse B cells could not be switched to the IgG2a class, even when presented with all the normal stimuli, and even though other IgG classes could be produced normally—or even in higher amounts. Even more surprisingly, in existing IgG2a memory B cells, the abrupt knockdown of T-bet levels caused the cells to lose their ability to respond to a new infection. In fact, most of the T-bet-deprived memory B cells became undetectable within a few days.
“T-bet turns out to be the central molecule that enforces the IgG2a class in B cells, and if its production stops in IgG2a memory cells, they become dysfunctional and die,” Wang said.

The finding that T-bet has this all-important, ongoing function in IgG2a memory cells suggested that other proteins play analogous roles in other classes of memory B cell. Wang therefore turned to memory B cells of the IgA class, and, with a similar set of experiments, showed that these memory B cells depend on the transcription factor RORα. “It essentially does for IgA memory cells what T-bet does for IgG2a memory cells,” said Wang.

Implications for Science and Medicine

Wang and McHeyzer-Williams and their colleagues are now searching for the proteins that keep other memory B cells healthy and in their classes. But already the work has clarified how memory B cells work. “Until now we haven’t really had a good conceptual framework for the development and maintenance of these cells,” McHeyzer-Williams said.

The findings clearly also have implications for medicine. By supplying a particular class-enforcement protein at the same time that it exposes B cells to microbial proteins, a vaccine could induce a long-term immunity that is heavily weighted towards a desired antibody class. “If you’re designing a vaccine for certain types of virus, for example, you would like to have lots of IgG2a and IgA memory cells,” said McHeyzer-Williams. “So the goal would be to design a chemical adjuvant for the vaccine that drives B cells into those classes.”

Similarly, therapies that knock down class-enforcement signals such as T-bet could usefully reduce or eliminate memory B cells in certain classes. “Some autoimmune, allergic and lymphoma conditions are driven by B cells of a particular class, for example IgE cells in allergies,” said McHeyzer-Williams. “Being able to target just that class of B cell would be an obvious advantage over existing therapies, such as steroids, that knock down large parts of the immune system.”

Other contributors to the paper, “Divergent Transcriptional Programming of Class-Specific B Cell Memory by T-bet and RORα,” were Louise J. McHeyzer-Williams and Shinji L. Okitsu of the McHeyzer-Williams lab; Thomas P. Burris of the Jupiter, Florida campus of Scripps Research, who provided crucial reagents for manipulating RORα levels; and Steven L. Reiner of Columbia University’s College of Physicians and Surgeons, who supplied transgenic mice.

Nathaniel Wang is a CTSA TL-1 scholar in association with the Scripps Translational Science Institute (STSI).

Professor McHeyzer-Williams’s research is funded in part by the National Institutes of Health.

About The Scripps Research Institute

The Scripps Research Institute is one of the world's largest independent, not-for-profit organizations focusing on research in the biomedical sciences. Over the past decades, Scripps Research has developed a lengthy track record of major contributions to science and health, including laying the foundation for new treatments for cancer, rheumatoid arthritis, hemophilia, and other diseases. The institute employs about 3,000 people on its campuses in La Jolla, CA, and Jupiter, FL, where its renowned scientists—including three Nobel laureates—work toward their next discoveries. The institute's graduate program, which awards Ph.D. degrees in biology and chemistry, ranks among the top ten of its kind in the nation. For more information, see www.scripps.edu.
For information:
Office of Communications
Tel: 858-784-8134
Fax: 858-784-8136
press@scripps.edu

Mika Ono | EurekAlert!
Further information:
http://www.scripps.edu

More articles from Health and Medicine:

nachricht Another reason to exercise: Burning bone fat -- a key to better bone health
19.05.2017 | University of North Carolina Health Care

nachricht Disrupted fat breakdown in the brain makes mice dumb
19.05.2017 | Rheinische Friedrich-Wilhelms-Universität Bonn

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Wafer-thin Magnetic Materials Developed for Future Quantum Technologies

Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.

Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...

Im Focus: World's thinnest hologram paves path to new 3-D world

Nano-hologram paves way for integration of 3-D holography into everyday electronics

An Australian-Chinese research team has created the world's thinnest hologram, paving the way towards the integration of 3D holography into everyday...

Im Focus: Using graphene to create quantum bits

In the race to produce a quantum computer, a number of projects are seeking a way to create quantum bits -- or qubits -- that are stable, meaning they are not much affected by changes in their environment. This normally needs highly nonlinear non-dissipative elements capable of functioning at very low temperatures.

In pursuit of this goal, researchers at EPFL's Laboratory of Photonics and Quantum Measurements LPQM (STI/SB), have investigated a nonlinear graphene-based...

Im Focus: Bacteria harness the lotus effect to protect themselves

Biofilms: Researchers find the causes of water-repelling properties

Dental plaque and the viscous brown slime in drainpipes are two familiar examples of bacterial biofilms. Removing such bacterial depositions from surfaces is...

Im Focus: Hydrogen Bonds Directly Detected for the First Time

For the first time, scientists have succeeded in studying the strength of hydrogen bonds in a single molecule using an atomic force microscope. Researchers from the University of Basel’s Swiss Nanoscience Institute network have reported the results in the journal Science Advances.

Hydrogen is the most common element in the universe and is an integral part of almost all organic compounds. Molecules and sections of macromolecules are...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Dortmund MST Conference presents Individualized Healthcare Solutions with micro and nanotechnology

22.05.2017 | Event News

Innovation 4.0: Shaping a humane fourth industrial revolution

17.05.2017 | Event News

Media accreditation opens for historic year at European Health Forum Gastein

16.05.2017 | Event News

 
Latest News

New approach to revolutionize the production of molecular hydrogen

22.05.2017 | Materials Sciences

Scientists enlist engineered protein to battle the MERS virus

22.05.2017 | Life Sciences

Experts explain origins of topographic relief on Earth, Mars and Titan

22.05.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>