The ‘bad apples’ of the immune system are also its secret weapon, according to major Australian research published today in the world-leading journal Science.

In a world first, scientists from Sydney’s Garvan Institute of Medical Research have revealed how a mysterious population of cells in the immune system—which are usually ‘silenced’ because they can harm the body—can provide crucial protection against invading microbes. The research was carried out in mice.

Until now, the cells were thought to be ‘bad apples’ because they each produce an antibody that attacks the body’s own tissues and can cause autoimmune disease.

The new findings reveal, for the first time, that the cells are a crucial part of the body’s immune defenses. Far from remaining silent, the cells can be rapidly ‘redeemed’—and then activated to attack—when the body is faced with a disease threat that other immune cells cannot tackle.

In the process of ‘redemption’, each cell rapidly acquires changes to the antibody gene it carries. Together, the changes mean that the cells can produce antibodies that no longer threaten the body—but instead become highly potent weapons to fight disease.

Importantly, antibodies from the redeemed cells are equipped to attack some of the trickiest microbes that the immune system faces: those that evade detection by disguising themselves to look like normal body tissue. Campylobacter, HIV, and other microbes disguise themselves as ‘self’, and are problematic targets for the immune system, which systematically avoids attacking ‘self’.

Because the antibodies in the redeemed cells started out as self-reactive, the improved versions have a powerful ability to recognize ‘almost-self’; so, the ‘bad apple’ cells represent a valuable untapped resource for the development of new vaccines against HIV.

Professor Chris Goodnow, who co-led the new research with A/Professor Daniel Christ (both of Garvan’s Immunology Division), says the new findings will fundamentally change thinking about how the immune system protects us.

“We once thought that harmful immune cells were discarded by the body—like a few bad apples in the barrel. Likewise, no one had any idea that you could start with a ‘bad’ antibody and make it good.

“From these new findings, we now know that every immune cell is precious when it comes to fighting invading microbes—and we’ve learned that the immune system recycles, conserves, and polishes up its ‘bad apples’ instead of throwing them away.”

“We’re excited about the impact of this new understanding on vaccine development,” adds A/Professor Christ. “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 have so far largely been ignored.”

This study was made possible by the generosity of The Bill and Patricia Ritchie Foundation, and through funding from the National Health and Medical Research Council (Australia) and the Australian Research Council.