Gene dose-dependent maturation and receptor editing of B cells expressing immunoglobulin (Ig)G1 or IgM/IgG1 tail antigen receptors

Conserved differences between the transmembrane and cytoplasmic domains of membrane immunoglobulin (Ig)M and IgG map alter the function of antigen rec eptors on naive versus memory B cells. Here, we compare the ability of thes e domains to signal B cell allelic exclusion and maturation ill transgenic mice. A lysozyme-binding antibody was expressed in parallel sets of mice as IgM, IgG1, or a chimeric receptor with ISM extracellular domains and trans membrane/cytoplasmic domains of IgG1. Like IgM, the IgG1 or chimeric IgM/G receptors triggered heavy chain allelic exclusion and supported development of mature CD21(+) B cells. Many of the IgG or IgM/G B cells became CD21(hi gh) and downregulated their IgG and IgM/G receptors spontaneously, resembli ng memory B cells and B cells with mutations that exaggerate B cell antigen receptor signaling. Unlike IgM-transgenic mice, "edited" B cells that earl y non-hen egg lysozyme binding receptors preferentially accumulated in IgG and IgM/G mice. This was most extreme in lines with the highest transgene c opy number and diminished in variant offspring with fewer copies. The sensi tivity of B cell maturation to transgene copy number conferred by the IgG t ransmembrane and cytoplasmic domains may explain the diverse phenotypes fou nd in other IgG-transgenic mouse strains and may reflect exaggerated signal ing.