International Immunology, Vol. 14, No. 6, pp. 577-584,
June 2002
© 2002 Japanese Society for Immunology
The variable, CH1, CH2 and CH3 domains of Ig heavy chain are dispensable for pre-BCR function in transgenic mice
1 Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720-3200, USA
Corresponding editor: M. S. Schlissel; E-mail: mss{at}uclimk4.berkley.edu
Transmitting editor: M. Bevan
The pre-BCR consists of Ig µ protein, the product of a heavy chain gene assembled by V(D)J recombination in pro-B cells, the surrogate light chains Vpre-B and 
5, and the signaling chains Ig
and Igß. Signaling by the pre-BCR is a checkpoint required for further maturation of pro-B cells in the adult bone marrow. However, it is currently not known whether an extracellular ligand is required to initiate pre-BCR signaling. We reasoned that if the ectodomain of the pre-BCR is required to interact with a ligand, then a truncated heavy chain protein would not support B cell development. To test this notion, we produced transgenic mice expressing a heavy chain protein whose extracellular domains except for CH4 were replaced by an irrelevant Ig superfamily ectodomain from the human CD8 protein. This transgene resulted in pre-BCR-like signaling since it rescued development of pre-B cells in recombinase-activating gene (RAG)1-deficient mice and resulted in allelic exclusion of the endogenous Ig heavy chain gene in RAG-proficient mice. These findings lead us to suggest that the majority of the extracellular region of the pre-BCR is not required for pre-BCR function and, thus, ligand binding is unlikely to be required for pre-BCR function.
Keywords: B cell development, pre-B cell receptor, allelic exclusion, V(D)J recombination, transgenic mouse
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