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Scripps Research scientists show how memory B cells stay 'in class' to fight different infections
Date:5/7/2012

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 nave 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 normallyor 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 mem
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Contact: Mika Ono
mikaono@scripps.edu
858-784-2052
Scripps Research Institute
Source:Eurekalert  

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Scripps Research scientists show how memory B cells stay 'in class' to fight different infections
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