Polymerization of IgA and IgM: Roles of Cys(309)/Cys(414) and the secretory tailpiece

We have investigated how the secretory tailpiece (tp), Cys(414) and the ami no acids Ranking Cys(414) Cys(309) are involved in regulating the different polymerization of IgM and IgA to pentamers and dimers/monomers, respective ly. Whereas changing the tp of IgM to that of IgA has little effect on IgM polymerization, introducing the mu tp to IgA leads to the formation of larg er than wild-type IgA polymers, including pentamers and hexamer. This shows that the secretory tp ran differentially regulate polymerization depending on the heavy chain context, Cys(414), which is engaged in intermonomeric d isulfide bunds in IgM, is not crucial for the difference in IgM and IgA pol ymerization; IgM with a C414S mutation forms more large polymers than IgA, Also, IgA with IgM-like mutations in the five amino acids flanking Cys(309) , which is homologous to Cys(414), oligomerize similarly as IgA wild type, Thus, IgA appears to have an inherent tendency to form monomers and dimers that is partially regulated by the tp, while the Cys(309) region has only a minor effect. We also show that complement activation by IgM is sensitive to alterations in the polymeric structure, while IgA is inactive in classic al complement activation even for polymers such as pentamers and hexamers.