A negative regulatory role for Ig-alpha during B cell development

The development of B cells requires the expression of an antigen receptor a t distinct points during maturation. The Ig-alpha/beta heterodimer signals for these receptors, and mice harboring a truncation of the Ig-alpha intrac ellular domain (mb-1(Delta c/Delta c)) have severely reduced peripheral B c ell numbers. Here we report that immature mb-1(Delta c/Delta c) B cells are activated despite tacking a critical Ig-alpha-positive signaling motif. As a consequence of abnormal activation, transitional immature IgM(high)IgD(l ow) B cells are largely absent in mb-1(Delta c/Delta c) mutants, accounting for the paucity of mature B cells. Thus, Ig-alpha cytoplasmic tail truncat ion yields an antigen receptor complex on immature B cells that signals con stitutively. These data illustrate a role for Ig-alpha in negatively regula ting antigen receptor signaling during B cell development.