Ontogeny of the secretory immune system: maturation of a functional polymeric immunoglobulin receptor regulated by gene expression.
In the rat, secretion of polymeric IgA from serum into bile is dependent upon the presence of a functional polymeric immunoglobulin receptor (pIgR) that acts as a hepatocyte plasma membrane receptor for ligand binding and as a transcellular transport molecule. The objective of this study was to document the developmental maturation and regulation of functionally intact rat liver pIgR. An adult pattern of IgA secretion was not detected until after day 23 postpartum (dPP), by using intravenously injected 125I-labeled dimeric IgA. Radioactive dimeric IgA was not detectable in hepatocyte transport vesicles until 21 dPP by electron microscopy autoradiographic analysis. By using a rabbit polyclonal antibody against the rat secretory component domain of the pIgR, Western blot analysis demonstrated that the plasma-membrane-bound pIgR levels in hepatocytes from rats aged 19-22 dPP increased 10-fold during this period. To determine whether or not this increase in membrane-bound pIgR reflected increased pIgR gene expression, we probed Northern blots of total cellular RNA extracted from neonatal rat liver with pIgR cDNA [GORF-1; Banting, G., Brake, B., Braghetta, P., Luzio, J.P. & Stanley, K. K. (1989) FEBS Lett. 254, 177-183]. The pIgR RNA levels between 19 and 22 dPP rose more than 20-fold and paralleled the increased membrane-bound pIgR protein during this same interval. These data demonstrate a developmentally regulated process that controls the ontogeny of biliary dimeric IgA secretion at the termination of the third week postpartum. The process appears to depend on the up-regulation of pIgR gene expression.
Huling
S
S
Department of Medicine, University of California, San Francisco 94121.
Fournier
G R
GR
Feren
A
A
Chuntharapai
A
A
Jones
A L
AL
D000375:Aging / Q000276:immunology*; D000818:Animals; D001345:Autoradiography; D002460:Cell Line; D002462:Cell Membrane / Q000276:immunology; D015342:DNA Probes; D005786:Gene Expression Regulation; D007070:Immunoglobulin A / Q000378:metabolism*; D007457:Iodine Radioisotopes; D008099:Liver / Q000254:growth & development* / Q000276:immunology; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D051381:Rats; D011916:Rats, Inbred F344; D011971:Receptors, Immunologic / Q000235:genetics*
D015342:DNA Probes; D007070:Immunoglobulin A; D007457:Iodine Radioisotopes; D011971:Receptors, Immunologic; D012313:RNA