The results presented in this study demonstrate that the immortalizing capacity of an inducible active STAT5 mutant can be used to obtain human, antigen-specific, monoclonal B cell lines, which have the capacity to undergo plasma cell differentiation. After turning off STAT5 these cells can then be induced to secrete immunoglobulins. By making use of memory B cells isolated from healthy donors we could screen for B cells that have been positively selected for high affinity against a specific antigen.