The human body plays host to trillions of microbes, and many of them live in our gastrointestinal tract; these microorganisms make up our gut microbiome. The immune system is built to recognize foreign invaders like bacteria in the body and attack them. The gut also has a critical role in the function of the immune system; while the gut and the microbes within it help us digest food and absorb nutrients, the gut also tamps down immune responses to microbes and molecules from food that may otherwise cause an immune response. It does so by churning out antibodies. So how does the gut use the immune system like that without destroying the gut microbiome?
Reporting in Nature, scientists have found that the portion of the immune system that is local to the gut is one that acts in a precise way, and can target specific microbes.
"It was thought that the gut immune system worked sort of like a general-purpose antibiotic, controlling every bug and pathogen," said Gabriel D. Victora, an immunologist and head of the Laboratory of Lymphocyte Dynamics. "But our new findings tell us that there might be a bit more specificity to this targeting."
This work suggested that the immune system has a significant influence on the composition of the gut microbiome, which is known to be closely linked to human health and disease.
"A better understanding of this process could one day lead to major implications for conditions where the microbiome is knocked out of balance," said Daniel Mucida, head of the Laboratory of Mucosal Immunology.
After encountering a pathogen like an invading bacterium, the B cells of the immune system’s germinal centers are able to learn to generate antibodies against the pathogen until one succeeds in binding to it and stopping it from causing further infection. This ‘winner clone’ B cell can then produce more cells, which go on to make more of these potent antibodies.
In this study, the researchers investigated how these types of B cells interact with the many bacteria living in the gut, which represent untold numbers of potential targets for the immune system. Using a mouse model, the scientists determined that around one in ten germinal centers in the gut were able to make winner clones. After examining the winners, the researchers found that the antibodies they make target specific species of gut bacteria.
Even in the gut, where a neverending stream of microbes is present, the immune system’s germinal centers can pick the winners.
"We can now investigate the winners and look at evolution in germinal centers as an ecological issue involving many different species, as we try to figure out the rules underlying selection in these complex environments," Victora said. "This opens up a whole new area of inquiry."