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

TitleB cell development is arrested at the immature B cell stage in mice carrying a mutation in the cytoplasmic domain of immunoglobulin beta.
Publication TypeJournal Article
Year of Publication2001
AuthorsReichlin A, Hu Y, Meffre E, Nagaoka H, Gong S, Kraus M, Rajewsky K, Nussenzweig MC
JournalJ Exp Med
Volume193
Issue1
Pagination13-23
Date Published2001 Jan 01
ISSN0022-1007
KeywordsAlleles, Animals, Apoptosis, B-Lymphocytes, Base Sequence, Calcium Signaling, Cell Differentiation, DNA Primers, Immunoglobulin D, Immunoglobulin M, Mice, Mice, Knockout, Mice, Transgenic, Mutation, Receptors, Antigen, B-Cell, Signal Transduction
Abstract

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 function of Ig beta, we produced mice that carry a deletion of the cytoplasmic domain of Ig beta (Ig beta Delta C mice) and compared them to mice that carry a similar mutation in Ig alpha (MB1 Delta C, herein referred to as Ig alpha Delta C mice). Ig beta Delta C mice differ from Ig alpha Delta C 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 Ca(2+) flux. However, Ig beta Delta C 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.

Alternate JournalJ. Exp. Med.
PubMed ID11136817
PubMed Central IDPMC2195879
Grant ListKO8 / / PHS HHS / United States