Published online 1 January 2001.
© The Rockefeller University Press, 0022-1007/2001/1/13/ $5.00
The Journal of Experimental Medicine, Volume 193, Number 1, January 1, 2001 13-24
B Cell Development Is Arrested at the Immature B Cell Stage in Mice Carrying a Mutation in the Cytoplasmic Domain of Immunoglobulin β
Amy Reichlina,
Yun Hua,
Eric Meffrea,
Hitoshi Nagaokaa,
Shiaoching Gonga,
Manfred Krausb,
Klaus Rajewskyb, and
Michel C. Nussenzweiga
a Laboratory of Molecular Immunology, Howard Hughes Medical Institute, The Rockefeller University, New York, New York 10021
b Institute for Genetics, University of Cologne, 50931 Cologne, Germany
Laboratory of Molecular Immunology, Howard Hughes Medical Institute, The Rockefeller University, 1230 York Ave., New York, NY 10021.212-327-8370212-327-8067
nussen{at}rockvax.rockefeller.edu
The B cell receptor (BCR) regulates B cell development and function through immunoglobulin (Ig)
and Igβ, 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 Igβ, we produced mice that carry a deletion of the cytoplasmic domain of Igβ (Igβ
C mice) and compared them to mice that carry a similar mutation in Ig
(MB1
C, herein referred to as Ig
C mice). Igβ
C mice differ from Ig
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 Ca2+ flux. However, Igβ
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 Igβ is required for B cell development beyond the immature B cell stage and that Ig
and Igβ have distinct biologic activities in vivo.
Key Words: B cell receptor immunoglobulin
immunoglobulin β immunoreceptor tyrosine activation motif apoptosis
A. Reichlin and Y. Hu contributed equally to this work.
Abbreviations used in this paper: BCR, B cell receptor; CGG, chicken gamma globulin; ITAM, immunoreceptor tyrosine activation motif; RAG, recombination activating gene; SH2, src homology 2.
© 2001 The Rockefeller University Press

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