Production of anti-phosphorylcholine antibodies of the T15 idiotype in CBA/N xid mice: Investigation of the defect using a T15 immunoglobulin transgene

Abstract

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 μg/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 I (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.