ALTERED HEPATIC TRANSPORT OF IMMUNOGLOBULIN-A IN MICE LACKING THE J-CHAIN

We have created J chain knockout mice to define the physiologic role o f the J chain in immunoglobulin synthesis and transport. The J chain i s covalently associated with pentameric immunoglobulin (Ig) M and dime ric IgA and is also expressed in most IgG-secreting cells. J chain-def icient mice have normal serum IgM and IgG levels but markedly elevated serum IgA. Although polymeric IgA was present in the mutant mice, a l arger proportion of their serum IgA was monomeric than was found in wi ld-type mouse serum. Bile and fecal IgA levels were decreased in J cha in-deficient mice compared with wild-type mice, suggesting inefficient transport of J chain-deficient IgA by hepatic polymeric immunoglobuli n receptors (pIgR). The pIgR-mediated transport of serum-derived IgA f rom wild-type and mutant mice was assessed in Madin-Darby canine kidne y (MDCK) cells transfected with the pIgR. These studies revealed selec tive 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 re quired for IgA dimerization, it does affect the efficiency of polymeri zation or have a role in maintaining IgA dimer stability. Furthermore, the J chain is essential for efficient hepatic pIgR transport of IgA.