The germinal center response
Protection from harmful microbes depends on the generation of pathogen-specific antibodies that can bind effectively pathogens and neutralize their activity. High-affinity antibodies originate from germinal centers, microanatomical sites that form within lymphoid organs in response to microbe invasion and vaccination. Naive B cells that carry an antibody on their surface circulate through the blood circulation and lymph nodes until they encounter a cognate antigen which triggers their activation and proliferation. Antigen-stimulated B cells can differentiate into germinal center B cells in lymphoid organs and improve the affinity of their surface antibody in a process known as antibody affinity maturation. Within the germinal center B cells change the sequence of their antibody-coding genes and generate mutated antibodies with different antigen-binding properties. Subsequently, the B cells are subjected to affinity selection by T cells which physically interact with the B cells. In our lab we are able to examine these interactions using an imaging technique that allows visualization of immune cells in intact lymphoid organs of living mice. We also employ whole-organ imaging approaches of draining lymph nodes using light sheet microscopy.
Our research involves employing imaging techniques to observe the supportive cells within the germinal center structure. By utilizing mice with macrophages fluorescently labeled, we have successfully visualized the elimination process of dead cells that were not chosen by T cells during the germinal center reaction. Additionally, we traced the origins of these cells and identified that they arise from resident precursors situated in lymph organs before vaccination or pathogen invasion. This sheds light on the dynamic processes of dead cell disposal in germinal centers and the role of resident precursors in these mechanisms.
In order to examine the differentiation stage of the cells and discover new molecular patterns, we use transgenic mice and single-cell RNA techniques to examine the factors that control cell differentiation, antibody affinity maturation and differentiation into antibody-forming cells and memory cells. We focus on several aspects that control gene expression, including chromatin remodeling and RNA modifications.
