The Journal of Experimental Medicine
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Published online 27 December 2000.
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© 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


Original Article

B Cell Development Is Arrested at the Immature B Cell Stage in Mice Carrying a Mutation in the Cytoplasmic Domain of Immunoglobulin ß

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

Correspondence to: Michel C. Nussenzweig, Laboratory of Molecular Immunology, Howard Hughes Medical Institute, The Rockefeller University, 1230 York Ave., New York, NY 10021. Tel:212-327-8067 Fax:212-327-8370 E-mail:nussen{at}rockvax.rockefeller.edu.

The B cell receptor (BCR) regulates B cell development and function through immunoglobulin (Ig){alpha} and Igß, 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 Igß, we produced mice that carry a deletion of the cytoplasmic domain of Igß (Igß{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). Igß{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 Ca2+ flux. However, Igß{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 Igß is required for B cell development beyond the immature B cell stage and that Ig{alpha} and Igß have distinct biologic activities in vivo.

Key Words: B cell receptor, immunoglobulin {alpha}, immunoglobulin ß, immunoreceptor tyrosine activation motif, apoptosis


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