B cell development is arrested at the immature B cell stage in mice carrying a mutation in the cytoplasmic domain of immunoglobulin beta

The B cell receptor (BCR) regulates B cell development and function through immunoglobulin (Ig)alpha and Ig beta, a pair of membrane-bound Ig superfam ily proteins, each of which contains a single cytoplasmic immunoreceptor ty rosine activation motif(ITAM). To determine the functional of Ig beta, we p roduced 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 be ta DeltaC Inicr differ from Ig alpha DeltaC mice in that they show little i mpairment in early B cell development and they produce immature B cells tha t 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 devel opment in the bone marrow and die by apoptosis. We conclude that the cytopl asmic 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 activiti es in vivo.