Late events in assembly determine the polymeric structure and biological activity of secretory IgM.
IgM antibodies can be secreted in at least two functional polymeric forms that can be distinguished according to subunit composition. While IgM hexamers comprise six H2L2 monomeric subunits, pentamers contain an additional polypeptide, the J chain. In the presence of high abundance J chain protein, IgM pentamers are preferentially assembled at the expense of hexamers. To determine the mechanism by which J chain regulates the assembly process, we defined the point at which J chain is added to assembling polymers. We found no evidence for the presence of J chain in small IgM assembly intermediates of IgM, suggesting that it was not stably associated with these complexes. However, J chain was found associated with large polymeric IgM complexes exhibiting sedimentation properties of intracellular pentameric structures. These complexes were frequently not completely covalently assembled; however, complete covalent assembly of J chain-containing pentameric complexes did occur prior to their maturation in the Golgi. These data argue that pentameric structures are the substrate for J chain incorporation into assembling IgM and suggest that the incorporation of J chain is thermodynamically favored over the addition of a sixth monomeric subunit into an assembling polymer. We conclude that late events in IgM polymer assembly, specifically the insertion of J chain, the exclusion of an additional monomeric subunit, and the covalent closure of the pentameric IgM molecule, determine the polymeric structure and, consequently, the biological activity of secreted IgM.
Brewer
J W
JW
Department of Microbiology, Boston University School of Medicine, MA 02118, U.S.A.
Corley
R B
RB
D000818:Animals; D001704:Biopolymers / Q000276:immunology / Q000378:metabolism; D006825:Hybridomas; D007144:Immunoglobulin J-Chains / Q000737:chemistry / Q000378:metabolism; D007075:Immunoglobulin M / Q000737:chemistry* / Q000378:metabolism* / Q000502:physiology; D007424:Intracellular Fluid / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D013329:Structure-Activity Relationship
D001704:Biopolymers; D007144:Immunoglobulin J-Chains; D007075:Immunoglobulin M; C033027:secretory IgM