Yale Researchers Discover New Role for B Cells/Discovery Might Shed Light on "Mad Cow Disease"

A Yale study reveals that B cells play a leading role in promoting the development of unique cells that serve as gatekeepers for disease in the gastrointestinal area.

B cells once were thought to function mainly as sources of serum antibody and as activators of T lymphocytes, said Mark Shlomchik, M.D., associate professor in the Department of Laboratory Medicine and the Section of Immunobiology, referring to the findings published Thursday in Science.

“This discovery also may explain why B cells are important in diseases such as retrovirus transmission, as described in our study, and Creutzfeldt-Jakob Disease (CJD), as reported by other researchers,” said Shlomchik. CJD is a human syndrome with similarities to bovine spongiform encephalopathy, or “Mad Cow Disease.”

“B cells were thought to simply produce antibodies and to activate T cells,” he said. “Now we know that B cells are required for the development of a cell called the ‘M’ cell, which is a component of the immune system specific to the gastrointestinal tract.”

Shlomchik said M cells mediate communication between the immune system and gastrointestinal flora, which include potential pathogens as well as normal organisms. “M cells play a role in sensitizing the immune system to such flora,” he said, “but they are also a portal of entry since many pathogens seem to enter the body through M cells.”

Shlomchik said that although B cells were known to be important in transmission of CJD in a mouse model, the leading explanation was that the B cell itself carried the agent.

This idea led many nations in the European Community to filter out white cells, including B cells, from the blood supply. “The blood community has recently started filtering all the white blood cells from blood collected in Europe, Japan and Canada, in part due to the belief that B cells were directly transmitting the (CJD) disease,” he said. “But our results show an unexpected, different and more plausible mechanism of action for B cells.”

“No one had expected a role like this – to direct the development of another cell, the M cell – for the B cell,” Shlomchik continued. “The M cell is clearly an important cell in mediating the interaction of the body and organisms normally in the gut.”

He said the researchers made the discovery while attempting to understand the role of B cells in the transmission of the mouse mammary tumor retrovirus.

Shlomchik said the researchers now will try to determine just how B cells promote M cell development and which organisms gain entry into the body via M cells.

Co-investigators of the study included Tatyana Golovkina and Alexander Chervonsky, both of the Jackson Laboratory, as well as Lynn Hannum, a graduate student who formerly worked with Shlomchik. The work extends a collaboration begun when Chervonsky was working in the laboratory of Charles A. Janeway Jr. at Yale University School of Medicine.

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