Infections may trigger autoimmunity via rare, but normal process

PHILADELPHIA - The body's immune system has sophisticated safeguards in place to prevent it from turning its destructive power against the body's own cells. Immune cells with the capability of attacking the self are readily identified in healthy individuals, and these cells are typically purged from the system. Autoimmune disorders, such as lupus, arthritis, and diabetes, are understood to result from breakdowns in those protections - they are seen as departures from the healthy norm.

New findings from researchers at The Wistar Institute, however, suggest that autoimmunity may result from the rare confluence of entirely normal events. A report on the results appears in the December 18 issue of the Journal of Experimental Medicine and is featured on the journal's cover.

The study tracked a mildly self-reactive subset of the body's so-called memory B cells - long-lived immune cells that stand ready to respond to pathogens the immune system has previously encountered. This B cell subset apparently evades detection by the immune system's screening against cells that attack self. Then, under certain circumstances, a subsequent viral infection can activate this group of cells to begin producing antibodies against self, perhaps triggering full-blown autoimmunity and disease.

"One thing this study tells us is that there doesn't appear to be any process that prevents memory B cells from generating responses to self," says Wistar associate professor Andrew J. Caton, Ph.D., senior author on the study. "It also tells us that a subsequent infection with a virus is quite capable of activating these self-reactive immune cells. It's not difficult to see how these events could lead to autoimmunity. The question then becomes how common this might be - could it explain a substantial proportion of autoimmune disease?"

Immunologists have long suspected that viral infections may be able to initiate autoimmune responses, but it has been difficult to design an experimen

Contact: Franklin Hoke/Marion Wyce
The Wistar Institute

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