Gabriel Victora, Ph.D.

Research

Antibodies are critical to immune protection against pathogens and to the effectiveness of vaccines, but they also mediate the more amicable interactions between the host and its commensal microbes. Work in the Victora lab focuses on various aspects of how antibody responses are constructed, with special emphasis on the germinal center reaction, where a Darwinian evolutionary process known as affinity maturation drives an increase in B cell and antibody affinity over time. Over the past decade, the Victora lab has been at the forefront of the study of the cellular and molecular mechanisms underlying affinity-based selection of B cells in germinal centers. The lab has also pioneered the study of clonal dynamics of the B-cell response, which seeks to understand how B-cell clonal diversity evolves in polyclonal systems, both with time and over repeated antigen encounters. These studies contributed to the field’s understanding of B-cell repertoire selection in infection and vaccination settings, and more recently, of the immune response to commensal microbiota in the gut.

As an Innovation Fund investigator, Gabriel Victora, Ph.D., is teaming up with Ilana Brito, Ph.D., to explore the interactions between gut microbiota and intestinal immune cells. The pair will focus on germinal centers, where specialized immune cells that produce antibodies, known as B cells, undergo selection and maturation to produce high-affinity antibodies. The project combines Brito’s expertise in microbiota multiomics and bacterial engineering with Victora’s extensive experience in germinal center biology and mouse biotechnology. Together, the team will identify antigen specificities of individual B cells using libraries of protein sequences from model microbiota. They will then use genetically engineered bacteria and mice to estimate the affinity of each B cell in a germinal center. Thus, they hope to determine which commensal species and antigens are targeted by the immune system, whether certain shared antigens allow the immune system to more efficiently target the vast array of bacteria in the intestine, and the extent to which affinity maturation to bacterial antigens occurs in the intestine.