Gabriel D. Victora, Ph.D.
Laurie and Peter Grauer Assistant Professor
Victora studies germinal centers, structures within lymphoid organs where antibodies mutate and improve their targeting capabilities. This process, called affinity maturation, 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. Antibody production creates an immunological memory that allows for a faster and more robust response to the invader upon subsequent exposures. It is also the basis for vaccination.
Antibodies are tuned to efficiently recognize a specific invader through affinity maturation, in which a small region of the antibody undergoes random hypermutation, followed by the proliferation of 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. His research could lead to more effective vaccines against pathogens such as influenza or HIV, and could help explain how affinity maturation can malfunction in diseases such as allergies.
In previous work, Victora developed techniques to label and observe cells within the lymph nodes of live mice, and was able to 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, unlike B cells, T cells are not physically restricted to individual GCs and can help maintain diversity in the antibody response.
To gain a deeper understanding of how high-affinity antibodies are generated and evolve during this complex process, the Victora lab is now 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 two fates—to remain within the GC or to differentiate into another 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, Victora and colleagues are investigating how different GCs within the same lymphoid organ may vary in terms of the antibodies they carry, and how these antibodies change over time to produce an effective antibody response.
By applying a broad scope in their work—from individual genes to the 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.