In humans, the CD27 + memory B cell population contains the majority of antigen-experienced B cells [23, 24] , and we reasoned that the same should be true in vaccinated HIS mice. We therefore cell sorted several different CD19 + CD27 + B cell subsets from individual HIS mice. We used two strategies to isolate the following human B cell (CD45 + CD19 + ) subsets from BM and spleens of vaccinated HIS mice: (i) CD27 hi CD38 hi , (ii) CD27 + CD38 lo/int IgD + , and (iii) CD27 + CD38 lo/int IgD 2 on the one hand ( Figure 3 - , although the number of cells was increased for each of these subpopulations in the vaccinated animals, as expected from the enhanced number of total B cells ( Table 2) . We only observed a significant increase in the frequency of IgG + B cells within the CD27 hi CD38 hi plasmablast population of vaccinated responder HIS mice, as compared to PBS-injected animals (13.262.7% and 4.361.8% of CD27 hi CD38 hi B cells, respectively; p = 0.0311). In order to identify, isolate and immortalize the antigen-specific antibody-producing B cells, the aforementioned B cell subsets were transduced immediately after cell sorting with a retroviral vector encoding both human BCL6 and BCL-XL [9, 19] . By ectopically expressing BCL6 and BCL-XL in splenic or peripheral blood memory B cells and culturing them with factors produced by follicular helper T cells (CD40L and IL-21), we generated highly proliferative, BCR positive B cell lines that secrete Igs. Since these cells express BCL6, the differentiation of memory B cells to terminal plasma cells is blocked [28, 29, 30] . Therefore, the resulting B cells can expand extensively in vitro for long periods of time in presence of CD40L and IL-21, and provide a tool to generate antigen-specific human BCR-positive, antibody-secreting B cell lines.