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Dr. Victora studies germinal centers, which are structures within lymphoid organs where antibodies mutate and improve their targeting capabilities in a process called affinity maturation. This allows the immune system to produce antibodies that are precisely targeted at invaders, resulting in faster and more robust responses upon subsequent exposures.

When a pathogen invades the human body, the immune system responds by producing proteins called antibodies that are precisely targeted at the invader. This creates an immunological memory that allows a faster and more robust response to the invader upon subsequent exposures, and is the basis for vaccination.

Antibodies are tuned to efficiently recognize a specific invader through a process called affinity maturation, in which a small region of the antibody undergoes random hypermutation, followed by proliferation of the mutants with high affinity to the pathogen. This process occurs in anatomical structures within lymphoid organs known as germinal centers (GCs), where B cells — the cells that produce antibodies — multiply and mutate. The Victora lab is currently investigating the mechanistic details of this process, which could lead to more effective vaccines against pathogens such as influenza and HIV, and help explain how this process can malfunction in diseases such as allergies.

By developing techniques to label and observe cells within the lymph nodes of live mice, Dr. Victora’s previous work has shed light on how B cells with high-affinity antibodies are selected and amplified. In addition to defining the types of B cells in GCs and their migration patterns, the research identified another major component of the immune system, T cells, as the regulators of this process. His work also showed that T cells, unlike B cells, are not physically restricted to individual GCs, which helps maintain diversity in the antibody response.

In order to gain a deeper understanding of how high affinity antibodies are generated and evolve during this complex process, the Victora lab is now focused on exploring three complementary perspectives: those of molecules, cells, and whole organs. On the molecular scale, research is underway to identify the key genes involved in how B cells choose between remaining within the GC or differentiating into a different cell type. At the cellular level, the lab is exploring how a cell’s history of interactions with other cells contributes to affinity maturation and GC development. Finally, Dr. Victora and colleagues are investigating how different GCs within the same lymphoid organ vary in terms of the antibodies they carry and how these antibodies change over time to produce an effective antibody response.

With the broad scope of this work, from genes up to dynamics within the spleen and lymph nodes, the Victora lab hopes to gain insight into the critical evolutionary processes by which the immune system refines its response to an infection or vaccine.