Immunoglobulin γ2b transgenes inhibit heavy chain gene rearrangement, but cannot promote B cell development

Abstract

Transgenic mice with a γ2b transgene were produced to investigate whether γ2b can replace μ in the development of B lymphocytes. Transgenic γ2b 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 γ2b-expressing B cells in the spleen also express μ. The same is true for mice with a hybrid transgene in which the μ transmembrane and intracytoplasmic sequences replace those of γ2b (γ2b-μmem). The B cell defect is not due to toxicity of γ2b since crosses between γ2b transgenic and μ transgenic mice have normal numbers of B cells Presence of the γ2b 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 μ locus is inactivated, B cells do not develop at all in γ2b transgenic mice. The data suggest that γ2b cannot replace μ 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.