Inactive Autoimmune B-cells May Play Role in Lymphoma Development

Inactive Autoimmune B-cells May Play Role in Lymphoma Development

New insights into the immunologic role of a specific type of B-cells — capable of autoimmune reactions but held in lockdown — may advance the understanding of how these cells contribute to the development of lymphoma.

The study, “IgD attenuates the IgM-induced anergy response in transitional and mature B cells,” published in the journal Nature Communications, also gives researchers a new understanding of how immune B-cells can respond to virtually any conceivable infection.

More than 20 years ago, Christopher Goodnow, professor and deputy director of Garvan Institute of Medical Research in Australia, discovered a population of B-cells that had an autoimmune potential, but were unreactive.

Even earlier, other researchers were pondering the existence of an antibody type called IgD. Unlike other antibodies, it was not clear what role IgD played in the immune system.

The findings by Goodnow and colleagues at another Australian institution — John Curtin School of Medical Research — show that IgD is responsible for preventing autoimmune reactions by the B-cells, yet allows them to contribute to responses against foreign invaders.

“We have known for some time that more than half of the immune system’s B-cells are capable of producing damaging antibodies against the body’s own tissues — yet they don’t do this,” Goodnow said in a news release.

“What we haven’t understood before is why and how the immune system keeps these potential ‘traitor cells’ alive instead of getting rid of them completely,” he said.

To better understand the workings of the cells, the research team examined the activity of all the genes in such a locked-down cell, comparing cells from mice that lacked IgD to normal mice. The study identified a set of more than 200 genes. A third of the genes turned out to be controlled by IgD and acted to prevent the cells from turning against the body’s own tissues.

IgD also directs the cells to gather in the spleen and lymph nodes together with other types of B-cells. If needed, IgD can contribute to the launch of an immune attack.

“We think that the large-scale lockdown of B-cells is the immune system’s way of avoiding ‘holes’ in its defensive line, so that it is ready to respond to any conceivable invasion,” Goodnow said. “If every B-cell capable of producing autoantibodies was removed rather than kept in lockdown, we would severely limit the number of foreign invaders that our immune system could recognize.”

The locked-down state of the cells is disturbed by mutations leading to lymphoma, and now researchers can begin to understand the processes in greater detail.

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