Mice with an inactivated joining chain locus have perturbed IgM secretion.

A mouse with an inactivated joining chain locus was produced by gene targeting in embryonic stem cells by deleting the first exon. Heterozygote (J+/-) and homozygote (J-/-) offspring from these mice showed normal total serum immunoglobulin levels and a normal peripheral B cell compartment when compared to wild-type littermates. The distribution of serum immunoglobulin isotypes in serum was different; IgA levels were elevated while IgM levels were reduced in J-/- mice as compared to wild-type mice. High molecular weight serum IgM was reduced in J+/- and J-/- mice and instead found in oligomeric form of undefined structure. Furthermore, serum IgM from J+/- and J-/- mice showed a reduced ability to activate complement. The number of splenic and bone marrow IgM plaque-forming cells were reduced in unimmunized J+/- as well as in J-/- mice. Furthermore, the number of plaque-forming cells was reduced in B cells from both J+/- and J-/- mice after stimulation with lipopolysaccharide in vitro. The perturbation of IgM production in J-/- mice appears to affect a late stage of differentiation, because cells with intracellular IgM were readily detected both in vivo and in vitro. Finally, after immunization with T-dependent or T-independent antigens the IgM component of the immune response was reduced in J-/- mice while only a marginal reduction of the IgG response was detected.