A Negative Regulatory Role for Ig-α during B Cell Development

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