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

The development of B cells requires the expression of an antigen receptor at distinct points during maturation. The Ig-alpha/beta heterodimer signals for these receptors, and mice harboring a truncation of the Ig-alpha intracellular domain (mb-1(delta(c)/delta(c)) have severely reduced peripheral B cell numbers. Here we report that immature mb-1(delta(c)/delta(c) B cells are activated despite lacking a critical Ig-alpha-positive signaling motif. As a consequence of abnormal activation, transitional immature IgMhighIgDlow B cells are largely absent in mb-1delta(c)/delta(c) mutants, accounting for the paucity of mature B cells. Thus, Ig-alpha cytoplasmic tail truncation yields an antigen receptor complex on immature B cells that signals constitutively. These data illustrate a role for Ig-alpha in negatively regulating antigen receptor signaling during B cell development.