Pax5 activates immunoglobulin heavy chain V to DJ rearrangement in transgenic thymocytes.
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 beta-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.
Hsu
Lih-Yun
LY
Division of Immunology, Department of Molecular and Cell Biology, University of California, Berkeley, 94720, USA.
Liang
Hong-Erh
HE
Johnson
Kristen
K
Kang
Chulho
C
Schlissel
Mark S
MS
D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D005434:Flow Cytometry; D015870:Gene Expression; D015322:Gene Rearrangement, B-Lymphocyte / Q000502:physiology*; D005803:Genes, Immunoglobulin / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D051757:PAX5 Transcription Factor; D016133:Polymerase Chain Reaction / Q000379:methods; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D019087:Selectins / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D013601:T-Lymphocytes / Q000502:physiology; D013950:Thymus Gland / Q000166:cytology / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D045567:VDJ Recombinases / Q000378:metabolism
D004268:DNA-Binding Proteins; D051757:PAX5 Transcription Factor; C497282:Pax5 protein, mouse; D011948:Receptors, Antigen, T-Cell; D019087:Selectins; D014157:Transcription Factors; D045567:VDJ Recombinases