Site-specific profiling of structure and function of IgM B cell receptor glycans

Although N-linked glycans play pivotal roles in the regulation of antibody effector functions, little is known about the composition and functional impact of glycans expressed by human B cell receptors (BCRs), likely due to technical challenges. Here, we describe the site-specific glycosylation profiles of all four N-linked glycosylation-sites of human IgM BCRs from primary naive and memory B cells. We show that the BCR glycans have not undergone structural changes during the transition from naive to memory cells. Moreover, using B cell lines expressing well-defined BCRs, we show that individual glycosylation sites are non-essential for cell-surface expression, and that the absence of the IgM BCR N209 glycan reduces the antigen-binding capacity of B cells. Collectively, these findings shows high conservation of IgM BCR glycosylation across IgM BCR B cell subsets and indicate a limited contribution to BCR expression and function, suggesting BCR glycans may have evolved to support IgM antibody functions.