Repertoire analysis in human immunoglobulin heavy chain minilocus transgenic, mu MT/mu MT mice

Mice transgenic for the human immunoglobulin heavy chain minilocus pHCl wer e developed several years ago to help better understand the mechanisms of V DJ recombination and antibody response. Interestingly, these minilocus tran sgenic mice develop a polyclonal, extremely diverse mu human immunoglobulin heavy chain repertoire, but when immunized, they exclusively use murine im munoglobulin heavy chains. Here, the data shows that when the minilocus is transferred by cross-breeding onto the mu MT background, the resulting mice (HCl-mu MT/mu MT mice) develop polyclonal, extremely diverse mu and gamma 1 human immunoglobulin heavy chain repertoires. Our data indicates that if no antigen specific antibodies are detected in pHCl transgenic mice, it is essentially due to competition with endogenous immunoglobulin heavy chain g ene segments. Moreover, the data shows that despite the presence of only on e functional V-H gene segment and despite mu and gamma 1 repertoires simila r to the early pre-immune human repertoire, HCl-mu MT/mu MT mice, can devel op immune responses against proteins and haptens. Finally, the data shows t hat in aged HCl-mu MT/mu MT mice, the generation of new B-cells may be impa ired and old mice may mainly rely on B-cell generated earlier in life to mo unt immune responses. Published by Elsevier Science Ltd.