The Journal of Experimental Medicine
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Published online 8 March 2004 doi:10.1084/jem.20032249
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 199, Number 6, 825-830
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Pax5 Activates Immunoglobulin Heavy Chain V to DJ Rearrangement in Transgenic Thymocytes

Lih-Yun Hsu1, Hong-Erh Liang1, Kristen Johnson2, Chulho Kang1, and Mark S. Schlissel1

1 University of California, Berkeley, Division of Immunology, Department of Molecular and Cell Biology, Berkeley, CA 94720
2 Department of Microbiology, Columbia University College of Physicians and Surgeons, New York, NY 10032

Address correspondence to Mark S. Schlissel, Div. of Immunology, Dept. of Molecular and Cell Biology, UC Berkeley, 439 LSA (#3200), Berkeley, CA 94720. Phone: (510) 643-2462; Fax: (510) 642-6845; email: mss{at}uclink4.berkeley.edu

Mice deficient for the B cell–restricted transcription factor Pax5 show a defect in the VH to DJH rearrangement step of immunoglobulin heavy chain gene assembly even though the expression of the V(D)J recombinase is not diminished in Pax5-/- pro–B cells. To investigate whether Pax5 is limiting for VH to DJH rearrangement, we generated transgenic mice which express Pax5 in developing thymocytes. We show that enforced expression of Pax5 in thymocytes results in a partial block in T cell development due to defective pre-TCR signaling in ß-selection. Moreover, our results demonstrate that expression of Pax5 in early thymocytes is sufficient to induce VH to DJH rearrangements in CD4+CD8+ T cells and lead us to suggest that Pax5 may play a direct role in the lineage-specific regulation of immunoglobulin heavy chain gene rearrangement.

Key Words: lymphocyte development • V(D)J recombination • gene expression regulation • transgenesis • immunoglobulin

The online version of this article contains supplemental material.

Abbreviations used in this paper: BSAP, B cell–restricted transcription factor Pax5; DN, CD4/CD8 double negative T cells; DP, CD4/CD8 double positive T cells; IgHC, Ig heavy chain; IgLC, Ig light chain; RSS, recombination signal sequence; LM, ligation-mediated.


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