Our immune system works to fight infections immediately, but also maintain long-term immunity. Two waves of protection help neutralize and eliminate disease, including the innate and adaptive immune responses. Innate immunity comprises of non-specific immune cells that recognize an invading pathogen and activate a broad response. This first wave of protection is responsible for initial inflammation and notifying the rest of the body of infection. The adaptive or second wave of immunity is more specific. Immune cells and antibodies are generated to recognize markers on pathogens. Not only does this arm of immunity eliminate infection, but it develops a memory to more readily target similar invaders in the future.
Two immune cells that make up the adaptive immune response include T and B cells. T cells are responsible for direct targeting of pathogens, whereas B cells help activate T cells and produce antibodies to inactivate viruses and other diseases. Once T and B cells come into contact with a disease, they develop specialized subsets of memory. As a result, the adaptive immune response will react to the same invading pathogen much faster, and the patient will not experience symptoms of illness. This is precisely how vaccines work. An attenuated or weakened form of a virus is injected into the body and the immune system fights it off. However, that pre-exposure to disease equips the immune system to be better prepared in the future.
Healthcare providers urge annual vaccinations because of the immune system’s adaptive response. Scientists work to identify the most prevalent flu virus each year to develop effective vaccines. Unfortunately, it is based on a predictive model, and is sometimes unclear which flu strain will become most prevalent. While vaccines help prevent disease, scientists are working to further improve their efficacy by understanding how specifically the immune system responds.
A recent article in Nature, by Dr. Michel Nussenzweig and others, demonstrates that B cells maintain advantageous mutations by proliferating under special circumstances. Consequently, this work has the potential to improve vaccine development for various diseases. Nussenzweig is a physician scientist and the Zanvil A. Cohn and Ralph Steinman Professor at Rockefeller University. He studies the molecular aspect of immunity, with a focus on adaptive immune response. Although his work encompasses cancer and cell biology, Nussenzweig currently investigates the B cell response to the SARS-CoV2 vaccine.
Nussenzweig and his team discovered for the first time that B cells bank favorable mutations by cloning themselves instead of continuing to mutate. As B cells develop, they mature and mutate to properly function. These random mutations can be advantageous, worthless, or deleterious. However, according to Nussenzweig’s team, the chance of B cells obtaining beneficial mutations is least likely. Further investigation revealed that B cells have a safeguard to obtain favorable mutations and maintain strong immunity.
Researchers mapped B cell lineages using sequencing analysis that identified genetic markers. Next generation sequencing technology has the capability to identify different cell populations in a sample. They additionally used other cell analyzing techniques and lab-based protocols, including animal models, to learn about B cell life cycle and how they provide effective immunity. As a result, the team identified internal mechanisms that drive B cell mutation and cloning. This discovery has the potential to develop vaccines that increase B cell mutation to develop antibodies for hard-to-treat targets or accelerate cloning to bank effective antibodies.
