The B cell receptor (BCR) regulates B cell development and function through immunoglobulin (Ig)alpha and Ig beta, a pair of membrane-bound Ig superfamily proteins, each of which contains a single cytoplasmic immunoreceptor tyrosine activation motif(ITAM). To determine the functional of Ig beta, we produced mice that carry a deletion of the cytoplasmic domain of Ig beta (Ig beta DeltaC mice) and compared them to mice that carry a similar mutation in Ig alpha (MB1 DeltaC, herein referred to as Ig alpha DeltaC mice). Ig beta DeltaC Inicr differ from Ig alpha DeltaC mice in that they show little impairment in early B cell development and they produce immature B cells that respond normally to BCR cross-linking as determined by Ca2+ flux. However, Ig beta DeltaC B cells are arrested at the immature stage of B cell development in the bone marrow and die by apoptosis. We conclude that the cytoplasmic domain Ig beta is required for B cell development beyond the immature B cell stage and that Ig alpha and Ig beta have distinct biologic activities in vivo.