Our bodies response to invading pathogens through different mechanisms of the immune system. Innate immunity first detects disease and relays a defense signal to activate the second wave of immune defense; adaptive immunity. This second line of protection elicits an immune response that is more potent and specific to the pathogen. The adaptive immune response is primarily made of two cell types including T cells and B cells. T cells are immune cells responsible for identifying the pathogen and targeting it. Interestingly, many immunotherapies focus on modulating the T cell response and redirecting the cells to the site of infection. B cells help activate T cells, but also produce antibodies against infections. These B or plasma cells work to neutralize foreign substances and allow the body to maintain homeostasis. Both T and B cells work together to orchestrate a strong immune response to resist disease.
Plasma cells are a common cell to target for therapy, and physicians and scientists rely on their proper function to build antibodies once we are exposed to low concentrations of disease. For example, the annual flu vaccine works by exposing the body to the predicted flu strain most prevalent for the year. In response to the vaccination, our bodies target the pathogen by activating T cells and stimulating plasma cells to produce antibodies specific for that flu strain. As a result, our bodies will become more prepared next time we encounter that specific flu virus. Although the healthcare community relies on plasma cells to fight disease, there is still a lot about their fundamental biology that is unclear. Scientists are working to learn more about their overall survival, migration patterns, and response to infection before and after exposure to pathogen.
A recent paper in the Journal of Experimental Medicine, by Dr. Tomohiro Kurosaki and others, demonstrated that proteins on plasma cells indicate that they are generated in the body to live months, years, and some an entire lifetime. This subset of plasma cells are primarily responsible for immune memory and fighting diseases previously exposed to the body. Kurosaki is a Team Leader at the RIKEN Center for Integrative Medical Sciences. His group investigates how immune cells mature and change based on their environment. Specifically, they focus on the characterization of T and B cells and understanding how they build immune memory.
Kurosaki and others have found how these long-lived plasma cells (LLPCs) are generated in lymphoid tissue and traffic to the bone marrow for longevity. To understand the underlying mechanism, scientists analyzed different proteins expressed on the surface of plasma cells. They compared these proteins from plasma cells recently produced in lymphoid tissue to plasma cells that successfully made it to the bone marrow. They discovered that a protein known as integrin beta-7 was a critical marker on plasma cells that determined their role as an LLPC.
Further investigation revealed that integrin beta-7 highly expressed on plasma cells migrated to the bone marrow and that it correlated with a protein, KLF2, which is necessary for cells to move from the lymphoid tissues to the blood. To demonstrate the direct link between integrin beta-7 and KLF2, scientists blocked KLF2 function and found that it inhibited the ability to resist disease, due to the lack of LLPCs present in the bone marrow.
Kurosaki and others for the first time uncovered an intracellular mechanism that drives a LLPC migration program and facilitates antibody response. This work has the potential to improve vaccinations and other therapies to boost immunity. Overall, the mechanism behind LLPC migration improves our understanding of plasma cell biology and can help the healthcare community better understand immune response to infection.
Paper, Journal of Experimental Medicine, Tomohiro Kurosaki, RIKEN
