Production of anti-phosphorylcholine antibodies of the T15 idiotype in CBA/N xid mice: investigation of the defect using a T15 immunoglobulin transgene.
A notable defect in CBA/N xid mice is their relative inability to make antibodies to phosphorylcholine (PC), particularly those of the T15 idiotype which predominate in the anti-PC responses of immunologically normal mice. To investigate the basis of this defect, we introduced functionally rearranged genes encoding a T15+ PC-binding immunoglobulin G antibody into the germline of these animals. Expression of these genes in the xid cells was observed, shown by the existence of a distinct population of T15+ cells (3 x 10(6)) in the spleen of the transgenic animals, and the presence of PC-binding T15+ IgG antibodies (1-15 micrograms/ml) in the serum. Mixed antibody molecules were also found, however, which were composed of both transgene-encoded and endogenously-derived chains. Existence of the T15+ cells in these animals seemed normal, since these were not depleted (to any great extent) and were immunocompetent as well. The latter was shown by the increased T15+ antibody production in the transgenic animals when stimulated with a PC-associated thymus-independent type 1 (TI-1) antigen and anti-idiotype antibodies, but not with the pneumococcal TI-2 antigen. This is similar to the PC-specific (T15-) responsiveness of normal CBA/N xid mice. Based on these results, we argue that a reason why T15+ antibodies are not normally made by CBA/N xid animals is because T15+ genes are not utilized or, as with any T15+ precursors present, selected for in these animals, in contrast to normal mice where the Lyb-5 or CD5 cells (which are absent in CBA/N xid animals) are known to be specially endowed to make such antibodies.
Lim
P L
PL
Clinical Immunology Unit, Chinese University of Hong Kong.
Chan
S T
ST
Leung
D T
DT
Ng
S S
SS
Loh
T T
TT
D000818:Animals; D000917:Antibody Formation; D001483:Base Sequence; D008040:Genetic Linkage; D007130:Immunoglobulin Idiotypes / Q000096:biosynthesis* / Q000235:genetics; D007153:Immunologic Deficiency Syndromes / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010767:Phosphorylcholine / Q000276:immunology*; D014960:X Chromosome
D007130:Immunoglobulin Idiotypes; D010767:Phosphorylcholine