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Repertoire analysis in human immunoglobulin heavy chain minilocus transgenic, muMT/muMT mice
1National Institutes of Health, National Eye Institute, Bethesda, MD 20892-1857, USA. tuaillon@intra.nei.nih.gov
Mice transgenic for the human immunoglobulin heavy chain minilocus pHCl were developed several years ago to help better understand the mechanisms of VDJ recombination and antibody response. Interestingly, these minilocus transgenic mice develop a polyclonal, extremely diverse mu human immunoglobulin heavy chain repertoire, but when immunized, they exclusively use murine immunoglobulin heavy chains. Here, the data shows that when the minilocus is transferred by cross-breeding onto the muMT background, the resulting mice (HCl-muMT/muMT mice) develop polyclonal, extremely diverse mu and gamma1 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 gene segments. Moreover, the data shows that despite the presence of only one functional V(H) gene segment and despite mu and gamma1 repertoires similar to the early pre-immune human repertoire, HCl-muMT/muMT mice, can develop immune responses against proteins and haptens. Finally, the data shows that in aged HC1-muMT/muMT mice, the generation of new B-cells may be impaired and old mice may mainly rely on B-cell generated earlier in life to mount immune responses.
Mice transgenic for the human immunoglobulin heavy chain minilocus pHCl were developed several years ago to help better understand the mechanisms of VDJ recombination and antibody response. Interestingly, these minilocus transgenic mice develop a polyclonal, extremely diverse mu human immunoglobulin heavy chain repertoire, but when immunized, they exclusively use murine immunoglobulin heavy chains. Here, the data shows that when the minilocus is transferred by cross-breeding onto the muMT background, the resulting mice (HCl-muMT/muMT mice) develop polyclonal, extremely diverse mu and gamma1 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 gene segments. Moreover, the data shows that despite the presence of only one functional V(H) gene segment and despite mu and gamma1 repertoires similar to the early pre-immune human repertoire, HCl-muMT/muMT mice, can develop immune responses against proteins and haptens. Finally, the data shows that in aged HC1-muMT/muMT mice, the generation of new B-cells may be impaired and old mice may mainly rely on B-cell generated earlier in life to mount immune responses.