Project 462807

Cell surface carbohydrates, referred to as glycans, cover all cells and play many important physiological roles. On immune cells, immunomodulatory glycan-binding proteins (GBPs) integrate signals from the outside of the cell to changes inside. Glycans can often undergo changes in their biochemical composition upon cellular differentiation. Such changes can be coupled to differential binding to GBPs, which may result in altered or specialized cellular functions unique to a given cellular differentiation state. Due to the complex biochemical nature of glycans, stemming from the structure of glycans not being directly controlled by the genetic code, deducing the function of altered glycosylation requires a comprehensive understanding of the changes in glycosylation and how these impact the GBP. One part of the adaptive immune response where pronounced changes in glycans are known to occur is in the germinal center, which is where antibody affinity maturation takes place following infection or vaccination. These changes in glycosylation are very pronounced and routinely used to identify the germinal center. Functional roles for these changes in glycosylation in the germinal center, however, are incompletely understood. Given that the germinal center is essential for immunity against a wide array of pathogens, it is essential to better understand this important immunological site. The two major immune cell types involved in the germinal center are the germinal center B cells and T follicular helper cells. Our lab has uncovered one role for changes in glycosylation on B cells in the germinal center, but it is equally important to assess the functional impact of changes in glycosylation on the T cells. This project will elucidate the functional roles played by changes in glycosylation on T follicular helper cells and how they impact cell-cell interactions with the B cells, which is a critically important step in antibody affinity maturation.