Although IgM mAbs might already be useful for some specific applications or could be modified by Ig class swapping to obtain IgG mAbs [36] , optimized humanized mouse models with improved B cell function are highly desirable. One reason for the suboptimal interaction of T and B cells may be the poor survival resulting in a high turnover of human T cells (discussed in [10, 37] ), making it very likely that procedures leading to improved accumulation of human T cells may promote B cell responses and isotype switching. It was already shown that human B cells undergoing isotype switching can be obtained in humanized mice, provided that a human environment supporting this process is present, e.g. in SCID mice transplanted with human fetal bones, thymus and lymph nodes [38] . Consistent with this notion, enhanced human peripheral T cell accumulation was observed in NOD/SCID mice transplanted with human bone marrow HSC, fetal liver and fetal thymus tissues (referred to as BLT mice), as compared to conventional humanized mouse systems [39] . Interestingly, BLT mice consistently generated an antigen-specific IgG response after HIV-infection [40] . Although it is yet unknown whether the isotype switch observed in BLT mice is truly T cell dependent, those data might support the idea that improved T cell homeostasis has a positive impact on B cell responses. To obtain humanized mouse models with improved B and T cell homeostasis, alternative strategies not relying on the transplantation of human fetal tissues -which are not necessarily easy to access to, for ethical, legal or practical reasons -will likely be favored in the future. The replacement of mouse genes involved in the hematopoietic system by their human equivalent is a valuable strategy to improve development, maintenance and/or function of several hematopoietic cell subsets in humanized mouse models, as shown with cytokines, such as IL-7 and Il-15 [15, 21, 41, 42] , or MHC molecules (N.D.H and J.P.D., manuscript submitted) [43, 44] . The fact that the human CD47 was shown to be unable to properly interact with the mouse SIRPa indicates that reintroducing a functional phagocyte inhibition mechanism via the CD47/SIRPa signaling axis is another strategy of potential interest [45] .