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. Transgenic gamma2b is present on the surface of B cells. Young transgenic 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 transgenic 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 expressed normally, and the early expression of transgenic light chains does not improve B cell maturation. When the endogenous mu locus is inactivated, B cells do not develop at all in gamma2b transgenic mice. The data suggest that gamma2b cannot replace mu in promoting the developmental maturation of B cells, but that it can cause feedback inhibition of heavy chain gene rearrangement. Thus, the signals for heavy chain feedback and B cell maturation appear to be different.