Altered hepatic transport of immunoglobulin A in mice lacking the J chain.
We have created J chain knockout mice to define the physiologic role of the J chain in immunoglobulin synthesis and transport. The J chain is covalently associated with pentameric immunoglobulin (Ig) M and dimeric IgA and is also expressed in most IgG-secreting cells. J chain-deficient mice have normal serum IgM and IgG levels but markedly elevated serum IgA. Although polymeric IgA was present in the mutant mice, a larger proportion of their serum IgA was monomeric than was found in wild-type mouse serum. Bile and fecal IgA levels were decreased in J chain-deficient mice compared with wild-type mice, suggesting inefficient transport of J chain-deficient IgA by hepatic polymeric immunoglobulin receptors (pIgR). The pIgR-mediated transport of serum-derived IgA from wild-type and mutant mice was assessed in Madin-Darby canine kidney (MDCK) cells transfected with the pIgR. These studies revealed selective transport by pIgR-expressing MDCK cells of wild-type IgA but not J chain-deficient IgA. We conclude that although the J chain is not required for IgA dimerization, it does affect the efficiency of polymerization or have a role in maintaining IgA dimer stability. Furthermore, the J chain is essential for efficient hepatic pIgR transport of IgA.
D000818:Animals; D001483:Base Sequence; D001646:Bile / Q000378:metabolism; D001692:Biological Transport; D002478:Cells, Cultured; D017931:DNA Primers / Q000737:chemistry; D004285:Dogs; D005803:Genes, Immunoglobulin; D007070:Immunoglobulin A / Q000737:chemistry / Q000378:metabolism*; D007144:Immunoglobulin J-Chains / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D046911:Macromolecular Substances; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D015183:Restriction Mapping
D017931:DNA Primers; D007070:Immunoglobulin A; D007144:Immunoglobulin J-Chains; D046911:Macromolecular Substances