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J. Biol. Chem., Vol. 280, Issue 18, 17807-17814, May 6, 2005

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Assembly of the PreB Receptor Requires a V-like Protein Encoded by a Germline Transcript^*

Roberto Rangel, Morgan R. McKeller¶, Jennifer C. Sims-Mourtada, Cristina Kashi, Kelly Cain, Eric D. Wieder||, Jeffrey J. Molldrem||, Lan V. Pham**, Richard J. Ford**, Patricia Yotnda, Christiane Guret, Véronique Francés, and Hector Martinez-Valdez¶¶

From the Department of Immunology, M. D. Anderson Cancer Center, The University of Texas, Houston, Texas 77054, the ^||Department of Blood and Bone Marrow Transplantation, Section of Transplant Immunology, M. D. Anderson Cancer Center, The University of Texas, Houston, Texas 77030, the ^**Department of Hematopathology, M. D. Anderson Cancer Center, The University of Texas, Houston, Texas 77030, the Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas 77030, and Schering-Plough, Laboratory for Immunology Research, 27 Chemin des Peupliers, 69571 Dardilly, Cedex, France

By confining germline transcription as a byproduct of the mechanisms inherent to genetic rearrangements, the translation of respective mRNAs and their biological relevance might have been overlooked. Here we report the identification, cloning, and biochemical characterization of a human V-like protein that is encoded by a germline transcript. This surrogate protein assembles with the immunoglobulin µ heavy chain at the surface of B cell progenitors and precursors to form a -like antigen receptor. These findings support the notion that germline transcription is not futile and stress the flexibility in eukaryotic gene usage and expression. In addition, the present study confirms the co-existence of surrogate and receptors that are proposed to work in concert to promote B lymphocyte maturation.

Received for publication, August 18, 2004 , and in revised form, March 3, 2005.

^* This work was supported by Grants 6161-03 from the Leukemia and Lymphoma Society and AI 056125-01 from the National Institutes of Health. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

H. M-V. dedicates the present work to the memory of the late Dr. Jacques Chiller. His friendship and his remarkable support to science will be forever remembered.

The on-line version of this article (available at http://www.jbc.org) contains supplemental material.

The nucleotide sequence(s) reported in this paper has been submitted to the GenBank^TM/EBI Data Bank with accession number(s) AJ004956.

Recipients of the Smith Predoctoral Fellowship.

^¶ Supported by the National Institutes of Health Training Grant T32 CA009598-15.

^¶¶ To whom correspondence should be addressed: Dept. of Immunology, Unit 902, The University of Texas, M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030. Tel.: 713-563-3212; Fax: 713-563-3357; E-mail: hmartine{at}mail.mdanderson.org.

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