In this paper we show that inactivation of STAT5 (by removing tamoxifen from the cultures) in the presence of IL-21 results in reappearance of immunoglobulin expression, although levels are still relatively low compared to levels normally described for ex vivo derived plasma cells. This suggests that the loss of immunoglobulin expression by primary B cells transduced with STAT5bER is dependent on activation of STAT5. We have found previously that activation of STAT5 in primary B cells inhibits the expression of Blimp-1. Blimp-1 is a transcription factor crucial for plasma cell differentiation [16, 34, 35] , and we here postulate that inactivation of STAT5 in our cell cultures leads to re-activation of Blimp-1 and subsequent differentiation of these cells into antibody secreting plasma cells.