Miles Holborough-Kerkvliet

Rheumatoid arthritis is characterized by an immune response to citrullinated (self)-antigens that is thought to be partly driven by anti-citrullinated protein antibody (ACPA) B cells. A peculiar feature of this response is that up to 90% of ACPA IgG contain variable domain glycans, compared to only 10% of total IgG. We hypothesize that these V-domain glycans are introduced to induce survival signals in ACPA B cells and bypass tolerance mechanisms by binding to glycan binding receptors. The aim of this study is to use engineered sialic acids carrying photo crosslinkers, to covalently tag and determine these receptors using mass spec and elucidate the mechanisms through which these V-domain glycans impact B cell receptor signaling.