A type of antibody long thought to have a minor role in immune system memory may actually be a key player, new findings suggest. Researchers tracked the antibody's function by imaging the immune system's B cells in the act of responding to a pathogen and developing into memory B cells, which can recognize an infectious agent years after first encountering it, they report in a study published online yesterday (October 25) in Nature Immunology.

B cell and memory B cell reacting to a virus Image: wikipedia

"I find this paper to be extremely interesting," said Wenxia Song, a professor of cell biology and molecular genetics at the University of Maryland who was not involved in the research. "The role of B cell memory is controversial. Now we can track B cell function in a way that has never been done before."

The B cells' principal function is to make antibodies against an antigen. B cells are activated when they recognize an antigen, and the activated cells then enter germinal centers -- located within lymph nodes or nodules -- where they can proliferate. The cells produce two classes of antibodies specific to the antigen. IgM antibodies, shaped like a ninja star, are usually released first to tag foreign antigens. The B cells are thought to then undergo a rearrangement of their genes to produce a second class of antibodies called IgG. Because IgG-producing cells can be found circulating in the blood for months after an infection, researchers have generally believed they were responsible for memory.

Jean-Claude Weill and his colleagues at the Institut National de la Santé et de la Recherche Médicale in Paris wanted to determine the precise function of B cells and how they become memory B cells by tracking the activity of individual B cells in mice. They created a novel in vivo technique to visualize B cells by injecting mice with a specific antigen tagged with a fluorescent protein marker. When B cells recognized the antigen, the fluorescent marker was activated. The researchers could then track the fluorescence to watch the B cells enter germinal centers and perform their functions in the cell.

Weill and his team characterized the activity of the marked B cells in the mice and then transferred the cells to a second set of mice that had been re-immunized with the antigen to probe B cell memory over a longer time period. In the germinal centers, they observed that some IgM cells switched to IgG memory cells, which mount the more significant antibody response, while other IgM cells continue to generate new memory B cells in germinal centers. The researchers also found that IgM memory cells persisted over the entire 12 months of the experiment, continuing to produce IgG memory cells during this time, whereas the number of IgG memory cells appeared to wane after 6 months. The cells' timeline suggested that IgM cells were critically involved in B cell memory.

"This study is important in terms of showing IgM B cells are more important in memory than we thought," said Stanley Plotkin, a vaccine specialist and a professor emeritus at the Wistar Institute and the University of Pennsylvania, who was not involved in the study.

Mark Shlomchik, a professor of laboratory medicine and immunology at Yale University, noted that the study is not the first to suggest a role for IgM cells in memory. "There is plenty of literature already identifying and characterizing IgM and IgG memory cells," he said. What's novel about this study, he added, is that the researchers could compare "different types of B memory cells head to head, which suggested that the primary function of IgG memory cells is to make antibodies while IgM memory cells seem to both make antibody-forming cells and to regenerate new memory cells."

Shlomchik pointed out, however, that the authors do not explain why IgM and IgG had these functions and noted that it's possible that IgM and IgG memory cells would have evolved different affinities, and thus have different functions upon a second exposure to that antigen.

Song agreed, noting that this study examines the function of B cells using just one type of antigen. "We'd need to verify these findings using other antigens," she said.


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