Linkage and assembly of polymeric IgA immunoglobulins

Abstract

The intersubunit linkage of polymeric IgA immunoglobulins was determined from studies of the products of reductive and cyanogen bromide cleavage. Under conditions of limited dithioerythritol reduction tetramer IgA molecules were cleaved to yield two monomers and a J chain containing dimer. The stability of the dimer and the conservation of the J chain disulfides indicated that the J chain joins two monomer subunits. Evidence confirming the J chain dimer clasp was obtained from the depolymerization of tetramer and dimer IgA by cyanogen bromide treatment. The cleavage studies also showed that (a) the S-S bonds directly joining the other subunits are located at the same penultimate alpha chain half-cystines that constitute the site of J chain attachment and (b) during limited reduction the monomer-monomer bonds undergo interchange to release subunits without a concomitant generation of alpha chain thiols. These linkage data provide strong support for the assembly of IgA and IgM polymers by sequential disulfide exchanges beginning with the formation of a J chain containing dimer.