Induction of pre-B cell proliferation after de novo synthesis of the pre-B cell receptor

Induction of pre-B cell proliferation after de novo synthesis of the pre-B cell receptor

^*Institut für Medizinische Strahlenkunde und Zellforschung (MSZ), University of Würzburg, Versbacher Strasse 5, D-97078 Würzburg, Germany; ^†Department of Physiological Chemistry, University of Ulm, Albert-Einstein-Allee 11, 89081 Ulm, Germany; ^‡Basel Institute of Immunology, Grenzacherstrasse 487, CH-4005 Basel, Switzerland; and ^§Division of Molecular Immunology, Department of Internal Medicine III, Nikolaus-Fiebiger-Center for Molecular Medicine, University of Erlangen-Nürnberg, Glückstrasse 6, D-91054 Erlangen, Germany

Edited by Frederick W. Alt, Harvard Medical School, Boston, MA, and approved December 5, 2000 (received for review October 17, 2000)

Abstract

The assembly of a pre-B cell receptor (pre-BCR) composed of an Ig μ heavy chain (μH-chain), the surrogate light (SL) chain, and the Igα/β dimer is critical for late pro-B cells to advance to the pre-B cell stage. By using a transgenic mouse model, in which μH-chain synthesis is solely driven by a tetracycline-controlled transactivator, we show that de novo synthesis of μH-chain in transgenic pro-B cells not only induces differentiation but also proliferation. This positive effect of μH-chain synthesis on proliferation requires the presence of SL chain and costimulatory signals provided by stromal cells or IL-7. We conclude that pre-BCR signaling induces clonal expansion of early pre-B cells.

Footnotes

↵ ¶ To whom reprint requests should be addressed. E-mail: twinkler{at}molmed.uni-erlangen.de.
This paper was submitted directly (Track II) to the PNAS office.
Article published online before print: Proc. Natl. Acad. Sci. USA, 10.1073/pnas.041492098.
Article and publication date are at www.pnas.org/cgi/doi/10.1073/pnas.041492098
Abbreviations:

H,

heavy chain;

L,

light chain;

pre-BCR,

pre-B cell receptor;

SL,

surrogate light;

RAG,

recombinant activating gene;

tetO,

tet-operator;

tTA,

tetracycline-controllable transactivator;

dTg,

double transgenic