IMMUNOGLOBULIN GAMMA-2B TRANSGENES INHIBIT HEAVY-CHAIN GENE REARRANGEMENT, BUT CANNOT PROMOTE B-CELL DEVELOPMENT

Transgenic mice with a gamma2b transgene were produced to investigate whether gamma2b can replace mu in the development of B lymphocytes. Tr ansgenic gamma2b is present on the surface of B cells. Young transgeni c mice have a dramatic decrease in B cell numbers, however, older mice have almost normal B cell numbers. Strikingly, all gamma2b-expressing B cells in the spleen also express mu. The same is true for mice with a hybrid transgene in which the mu transmembrane and intracytoplasmic sequences replace those of gamma2b (gamma2b-mumem). The B cell defect is not due to toxicity of gamma2b since crosses between gamma2b trans genic and mu transgenic mice have normal numbers of B cells. Presence of the gamma2b transgene strongly enhances the feedback inhibition of endogenous heavy chain gene rearrangement. Light chain genes are expre ssed normally, and the early expression of transgenic light chains doe s not improve B cell maturation. When the endogenous mu locus is inact ivated, B cells do not develop at all in gamma2b transgenic mice. The data suggest that gamma2b cannot replace mu in promoting the developme ntal maturation of B cells, but that it can cause feedback inhibition of heavy chain gene rearrangement. Thus, the signals for heavy chain f eedback and B cell maturation appear to be different.