We've all seen movies where the "bad guy" turns over a new leaf and becomes the "good guy." Is the same true for the immune system? Well, researchers from the Garvan Institute of Medical Research have found that those bad antibodies that can cause an autoimmune reaction can turn over a new leaf and protect against invading microbes. The findings were published today in Science.
How does the immune system attack microbes that look identical to itself without actually attacking itself? To answer that question, the group looked at silenced B cells, which are known to produce the bad antibodies.
"The big question about these cells has been why they are there at all, and in such large numbers," says Chis Goodnow, who co-led the work with Daniel Christ. "Why does the body keep these cells, whose antibodies pose a genuine risk to health, instead of destroying them completely, as we once thought?"
"We've shown that these silenced cells do have a crucial purpose, says Deborah Burnett, a Ph.D. student at Garvan whose work forms the basis of the study. "Far from 'clogging up' the immune system for no good reason, they're providing weapons—bad apples made good—to fight off invaders whose 'wolf in sheep's clothing tactics make it almost impossible for the other cells of the immune system to fight them."
The team found that the silenced B cells were capable of producing antibodies when they come across a foreign invader that acts as a wolf in sheep's clothing. So if the B cells normally create antibodies that cause an autoimmune response, how do they in response to foreign microbes, avoid attacking itself?
Well, it appears that before the cells attack, the antibodies they create go through a redemption process. During this redemption process, alternations are made to the antibody's DNA sequence. The first change stops the antibody from attacking itself and the other two increase the antibody's capability of binding to the invader. The three DNA changes alter the tips of the antibodies to improve the detection of invaders and dampen its ability to recognize 'self.'
"This research has taken us on an exciting journey," says Christ. "Not only have we uncovered a new kind of immunity, we've been able to confirm precisely how a bad antibody can be made good. Our findings indicate that there's a whole class of B cells out there—the silenced B cells—that might be accessible for vaccine development, and that we have so far largely ignored."
"We're hoping that, instead of ignoring this population of silenced B cells, researchers will in the future consider targeting these cells when they're developing vaccines, particularly against targets such as HIV, which disguise themselves as 'self'," says Burnett.