The carboxyl-terminal domains of IgA and IgM direct isotype-specific polymerization and interaction with the polymeric immunoglobulin receptor.
Mucosal surfaces are protected by polymeric immunoglobulins that are transported across the epithelium by the polymeric immunoglobulin receptor (pIgR). Only polymeric IgA and IgM containing a small polypeptide called the "joining" (J) chain can bind to the pIgR. J chain-positive IgA consists of dimers, and some larger polymers, whereas only IgM pentamers incorporate the J chain. We made domain swap chimeras between human IgA1 and IgM and found that the COOH-terminal domains of the heavy chains (Calpha3 and Cmu4, respectively) dictated the size of the polymers formed and also which polymers incorporated the J chain. We also showed that chimeric IgM molecules engineered to contain Calpha3 were able to bind the rabbit pIgR. Since the rabbit pIgR normally does not bind IgM, these results suggest that the COOH-terminal domain of the polymeric immunoglobulins is primarily responsible for interaction with the pIgR. Finally, we made a novel chimeric IgA immunoglobulin, containing the terminal domain from IgM. This recombinant molecule formed J chain-containing pentamers that could, like IgA, efficiently form covalent complexes with the human pIgR ectodomain, known as secretory component.
Braathen
Ranveig
R
Laboratory of Immunohistochemistry and Immunopathology, Institute of Pathology, University of Oslo, Rikshospitalet, N-0027 Oslo, Norway. ranveig.braathen@labmed.uio.no
Sorensen
Vigdis
V
Brandtzaeg
Per
P
Sandlie
Inger
I
Johansen
Finn-Eirik
FE
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers; D019281:Dimerization; D004285:Dogs; D006801:Humans; D007070:Immunoglobulin A / Q000737:chemistry* / Q000276:immunology; D007132:Immunoglobulin Isotypes / Q000737:chemistry* / Q000276:immunology; D007075:Immunoglobulin M / Q000737:chemistry* / Q000276:immunology; D007668:Kidney; D046911:Macromolecular Substances; D051379:Mice; D011817:Rabbits; D019056:Receptors, Polymeric Immunoglobulin / Q000276:immunology / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000276:immunology / Q000378:metabolism; D013552:Swine
D017931:DNA Primers; D007070:Immunoglobulin A; D007132:Immunoglobulin Isotypes; D007075:Immunoglobulin M; D046911:Macromolecular Substances; D019056:Receptors, Polymeric Immunoglobulin; D011993:Recombinant Fusion Proteins