The C(H)1 and transmembrane domains of mu in the context of a gamma 2b transgene do not suffice to promote B cell maturation

Mice carrying a gamma 2b transgene have been shown previously to be deficie nt in a cell development. In particular, a developmental block exists at th e pre-B cell stage. The few a cells that develop all express endogenous mu heavy chains, The phenotype suggests that gamma 2b exerts a strong feedback inhibition on endogenous Ig gene rearrangement, but, unlike mu, cannot sup port further a cell development. In this study we have created hybrid trans genes between gamma 2b and mu. Transgenic mice with a C(H)1 domain of mu, o r both a C(H)1 and transmembrane/cytoplasmic domain of mu replacing the res pective domains of a gamma 2b transgene, have the same a cell defect as gam ma 2b transgenic mice. Interestingly, the severity of the defect is correla ted with the level of expression of the transgene, suggesting that the degr ee of feedback inhibition of Ig gene rearrangement depends on the level and timing of Ig production. Crossing the gamma 2b/mu transgenes into a Bcl-x( L) transgenic line allows immature gamma 2b a cells to survive, but not to develop to maturity. Therefore, the missing function of mu is not simply an anti-apoptotic effect.