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 β-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.