Thesis Jana Koers

Summary

In this thesis, we describe how glycans can contribute to repertoire diversification and classification on both B cell subsets and antibodies. The results presented in this thesis support that glycans can be considered an undistinguishable part of the immunological repertoire through diversity generation and subset classification. We found that glycan profiles can give insight in the phenotypic and functional progression from differentiating B cell subsets and we describe novel patterns and biases of the acquisition of antibody Fab glycosylation during health and disease. The majority of Fab glycans is introduced by somatic hypermutation at predictable locations surrounding the antigen-binding site of antibodies and are introduced to various degrees during antibody responses depending on the antigen, antigen-context as well as Ig isotype/subclass. These findings increase our understanding of the role for Fab glycans in immunity, specifically in the context of B cell-mediated autoimmune diseases. Our findings suggest that future research on mapping cellular and antibody glycan profiles could be very useful, for example to improve B cell subset classification and to determine whether monitoring of Fab glycans can aid in diagnostics and disease progression and their contribution to pathogenesis. Moreover, the introduction of Fab glycans is a potential new avenue to be explored for improving new or existing therapeutic antibodies.