The production of high-affinity monoclonal antibodies (mABs) is genera
lly restricted to antigens recognised as foreign by the immune system.
Here we report the generation of mouse mABs specific for mouse IgD. M
ice rendered IgD-deficient by gene targeting and consequently immunolo
gically fully responsive to mouse IgD, were used to elicit a humoral r
esponse against mouse IgD. Hybridomas producing mABs of high affinity
were isolated and clones specific for non-allotypic determinants on th
e Fc or Fab portion of mouse IgD were obtained. The data show that mic
e lacking a protein of interest due to targeted gene inactivation can
be utilised for the production of high-affinity mABs specific for that
mouse protein and should also facilitate the generation of mABs speci
fic for proteins highly conserved between species.