The decline in immunoglobulin secretion corresponded with a decline in surface immunoglobulin expression [17] . This shows that with time, constitutive expression of STAT5 in human B cells leads to diminished expression and secretion of immunoglobulins. We questioned whether these effects could be reversed by deactivation of constitutively active STAT5 through removal of tamoxifen from the culture. We cultured the cells with tamoxifen, IL-2 and IL-4 for weeks to months until immunoglobulin production had vanished and then removed tamoxifen from the culture. In these cultures, when treated with IL-2 and IL-4 immunoglobulin secretion remained low or absent ( Figure 2 ), but when they were treated with IL-21, IgM or IgG immunoglobulin secretion resumed (Figure 2 and Figure S1 ). The immunoglobulin secretion lasted for about 7 days ( Figure S2 ). After approximately 14 days antibody production came to an end and the transduced B cells died [16] . It has been shown previously that IL-21 induces differentiation of B cells into plasma cells, but this was not observed in our B cells when STAT5 was active [18, 24, 25] . Together these data support the idea that IL-21 (but not IL-2 in combination with IL-4) induces strong plasma cell differentiation, which can be prevented by activation of STAT5 [16, 18, 24, 25] . Interestingly, our B cell lines maintained the capacity to secrete immunoglobulin after prolonged culture (weeks to months) and even after freeze thawing ( Figure S3 ).