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.
Department of Cellular and Molecular Immunology, Lunds University, Lund, Sweden.
L
L
Erlandsson
K
K
Andersson
M
M
Sigvardsson
N
N
Lycke
T
T
Leanderson
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology; D002454:Cell Differentiation; D003167:Complement Activation; D005260:Female; D018390:Gene Targeting; D006579:Heterozygote; D006720:Homozygote; D007114:Immunization; D007074:Immunoglobulin G / Q000097:blood / Q000235:genetics; D007132:Immunoglobulin Isotypes / Q000097:blood / Q000235:genetics; D007133:Immunoglobulin Joining Region / Q000235:genetics*; D007075:Immunoglobulin M / Q000097:blood* / Q000737:chemistry / Q000235:genetics*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008970:Molecular Weight; D010950:Plasma Cells / Q000166:cytology / Q000276:immunology
D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; D007133:Immunoglobulin Joining Region; D007075:Immunoglobulin M; D008070:Lipopolysaccharides