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 V-H to DJ(H) 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 V-H to DJ(H) 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 V-H to DJ(H) 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.