Researchers at Penn State College of Medicine have uncovered a surprising new role for B cells, the immune cells best known for producing antibodies. In response to flu infection, a specialized group of B cells in the germinal center of lymph nodes were found to produce interleukin-1 beta (IL-1β), a cytokine previously thought to be restricted to the body’s innate immune cells. This discovery shows that B cells not only contribute to antibody production but also play a critical part in coordinating robust, long-term immune responses. The study, published in PLOS Pathogens, highlights a potential paradigm shift in our understanding of adaptive immunity and points to new targets for enhancing vaccines particularly against influenza as well as future treatments for cancer and autoimmune diseases.

When a pathogen such as the flu virus enters the body, it triggers a chain of immune responses. The first line of defense, known as innate immunity, responds quickly to fight the infection and limit its spread. Meanwhile, the body activates adaptive immunity involving B cells and T cells which takes longer to develop but is essential for long-term protection. Adaptive immunity not only remembers pathogens but also ensures faster and stronger responses upon future encounters. Central to this process are germinal centers within the lymph nodes, which form during infection or vaccination. These specialized sites serve as training grounds where germinal center B cells rapidly multiply, adapt, and refine themselves to produce highly targeted antibodies and long-lasting memory B cells.

Allie explained that the lab’s focus is on improving germinal center function to generate stronger, more protective memory B cells, since longer-lasting germinal centers lead to better immunity. The study revealed that interleukin-1 beta is essential for sustaining high-quality germinal centers because it supports T follicular helper (TFH) cells, which are necessary for their persistence. Without this cytokine, TFH cells are reduced, and germinal centers shrink. Importantly, the researchers found that germinal center B cells themselves produce interleukin-1 beta and supply it to TFH cells uncovering a previously unknown two-way interaction that enhances the quality and effectiveness of germinal centers.

While B cells are best known for producing antibodies, this study shows they also act as helper cells, supporting other immune cells and playing a vital role in the function of T follicular helper (TFH) cells and germinal centers, explained first author Juliana Restrepo Munera. Using both a mouse model of influenza and human B cells, the team demonstrated that germinal center B cells generate interleukin-1 beta through the NLRP3 inflammasome, a protein complex typically associated with innate immunity. This finding reveals that the inflammasome and interleukin-1 beta are active in GC B cells but not in other B cells, and without them, TFH cells cannot function effectively, leading to poorly developed germinal centers

Restrepo Munera noted that these findings open possibilities for boosting immune responses by targeting the NLRP3 inflammasome pathway or GC B cell–derived interleukin-1 beta to extend germinal center activity. Such approaches could guide the development of more effective flu vaccines against ever-changing viruses and offer new strategies to better regulate immune responses in diseases like cancer and autoimmune disorders.

Source: https://www.psu.edu/news/research/story/antibody-making-cells-reveal-new-function-response-flu-infection