Researchers uncovered an unusual feature of bat immunity that could help to explain how these mammals evade infections. Vesper bats, the world's largest family of bats, may possess two separate genetic systems for producing the building blocks of antibodies, the immune proteins that latch onto germs. This configuration has never been found before in mammals.
The findings, published Wednesday (July 29) in the journal Science Advances, could open new avenues for studying viral infections and the evolution of immunity.
'More diversity in their antibodies'
Antibodies are Y-shaped proteins that help the immune system recognize and neutralize foreign invaders, including viruses, as well as other threats, like toxins. Each antibody contains two "heavy chains" and two "light chains," structures that work together to recognize and bind to specific features of viruses, bacteria or other targets.
In humans and most other mammals, the genes that build antibody heavy chains are organized into a single region of the genome, called a locus. Cells create a wide range of antibodies by mixing and matching the proteins encoded in different segments of that locus.
However, Frank's collaborator and former graduate student Dr. Taylor Pursell thought the finding might be genuine, rather than an experimental fluke.
Hannah Frank holds a bat skeleton in her laboratory. (Image credit: Kenny Lass/Tulane University)
Using genetic analysis, the team found that one of the two loci contained a larger and more varied collection of gene segments that could be used to create a broad, ready-made repertoire of antibodies. The other had fewer of these building blocks but appeared to rely more heavily on a process called somatic hypermutation, in which antibody-producing cells make small genetic changes after encountering a pathogen.
She compared this system to the different layers of defense seen in the 1998 Disney movie "Mulan." Upon seeing invaders at the Great Wall of China, guards raised an alarm to alert others without yet knowing the specific threat; this is like the innate immune system, the body's first, broad line of defense. The adaptive immune system is more like the heroine Mulan: highly targeted and capable of responding to a specific enemy, but slower to develop.
Michael Letko, molecular virologist at Washington State University
From each loci, bats can create a "cache of trainable, customizable cells," Frank said. This degree of customization could help the bats immune system ward off a wider range of threats than other mammals can.
Letko added that the genetic analysis in the study was impressive and lends credibility to the results. "It is hard to dispute the validity of information solidly founded on the genetic organization of these bats," he said.
"We think this discovery is an important piece of the puzzle," Frank said in a statement. "It doesn't fully explain why bats are such effective viral reservoirs, but it reveals a level of immune variety we didn't know existed and gives us an entirely new direction to explore."
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While bats are often viewed through the lens of the infectious diseases they carry, their story is far more complex, Frank said.
"Let's learn from the guys who've been evolving with them [viruses] for millions and millions of years," Frank said. "But let's try not to villainize them for surviving for millions and millions of years."
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