Biogenesis and function of IgM: the role of the conserved mu-chain tailpiece glycans

The tailpiece of secretory Ig-μ-chains (μ s tp) is highly conserved throughout evolution: in particular, a carboxy-terminal cysteine residue (Cys575) and a glycan linked to Asn563 are found in all species sequenced so far. Here we show that the μ s tp oligosaccharide moieties are important for the binding of J-chains and for the process of IgM polymerization. In the absence of the μ s tp glycans, pentamers cannot be assembled and polymers containing six or more subunits are secreted. Despite their increased valency, these molecules have a lower association rate with antigen than wild-type polymers. Unexpectedly, the C-terminal oligosaccharides also affect kinetic parameters on unpolymerized subunits. Thus, monomers lacking the C-terminal sugars because of either site-directed mutagenesis or selective enzymatic deglycosylation with endoglycosidase H, have a lower k on for the antigen. Taken together, our results indicate that the C-terminal μ -chain glycans can shape the structure of μ s2 L 2 subunits and their further assembly into polymers.