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PMID: 11136817 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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

The Journal of experimental medicine ·Vol. 193 ·No. 1 ·2001-01-01 ·Pages 13-23

Reichlin A, Hu Y, Meffre E, Nagaoka H, Gong S, Kraus M, Rajewsky K, Nussenzweig MC

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.

MeSH Terms
Alleles Animals Apoptosis/genetics,immunology B-Lymphocytes/cytology,immunology,metabolism Base Sequence Calcium Signaling/genetics,immunology Cell Differentiation/genetics,immunology DNA Primers/genetics Immunoglobulin D/biosynthesis Immunoglobulin M/biosynthesis Mice Mice, Knockout Mice, Transgenic Mutation Receptors, Antigen, B-Cell/genetics Signal Transduction/genetics,immunology
Chemicals
DNA Primers Immunoglobulin D Immunoglobulin M Receptors, Antigen, B-Cell
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Reichlin A
Laboratory of Molecular Immunology, Howard Hughes Medical Institute, The Rockefeller University, New York, New York 10021, USA.
Hu Y
Meffre E
Nagaoka H
Gong S
Kraus M
Rajewsky K
Nussenzweig M C
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
Published
2001-01-01
Pages
13-23
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2195879
Subset
IM
Grants
PHS HHS · KO8 · United States
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