It is also possible that soluble CD23 forms could directly or indirectly affect the anaphylactic process. It could be interesting to verify our results by analysis of IgE-mediated anaphylaxis in CD23 over expressing transgenic mice [41]. In addition it has been shown that, while CD23 is not expressed on basophils, its expression on B cells might control the size of the free IgE pool [31]. However, our immunization/sensitization experiments suggest

that the main difference in specific IgE production results from the IgE knock-in and not from the CD23 deficiency. With regard to anaphylaxis our data suggest that in a low level IgE production in IgEwt/wt CD23−/− mice the depletion of basophils Caspase inhibitor has comparable little influence on anaphylaxis. However, in the strong active immunization induced antigen-specific IgE response, in both IgEki/wtCD23−/− and IgEki/kiCD23−/− mice, basophil depletion reduces the anaphylaxis symptoms. Therefore, we postulate that basophils need a complex, polyclonal IgE dominated sensitization selleck chemicals llc to act in systemic anaphylaxis, which is probably not reached in passive IgE sensitization

in vivo [38]. The second aspect of the IgE knock-in mice is the lack of IgE+ B cells in vivo. The in vitro experiments demonstrate that stimulation of B cells is able to result in high levels of chimeric IgE expression as membrane bound IgE+ (mIgE) on B cells. The lack of the IgE+ B cells in vivo, in Nb infected mice, implies that either a molecule, which is essential for the expression of mIgE is missing or that an active suppressing factor is inhibiting the expression of membrane IgE+ B cells. Whether this observation is merely a genetic artifact or involves unknown IgE regulating mechanism in vivo needs to be addressed

in future experiments. Nevertheless targeting of IgE by monoclonal antibodies has become a part of human allergy therapy and might benefit from a better understanding of the in vivo expression or location of membrane IgE-positive cells. Finally, recent data by Yang et al. [11] could partially explain this phenotype by a rapid differentiation of an IgE+ B cell into a short-lived plasma B cell. In summary, we present data on a novel in vivo model allowing a more basic approach to examine genetic effects on the regulation Casein kinase 1 of IgE expression. Its usefulness extends our basic understanding of anaphylaxis by suggesting that IgE sensitization of basophils leads to most severe systemic anaphylaxis reactions. Moreover, this model may become a useful tool in decoding the still enigmatic “beneficial role of IgE” in immune homeostasis [20]. We cloned the IgG1 and IgE heavy chain, isolated from129Sv genomic DNA (Supporting Information Fig. 3) and inserted between the last exon for soluble IgG1 and the transmembrane exons a loxP site, and after the last exon for soluble IgE a neomycin resistance cassette (NeoR) and the thymidine kinase (Tk) framed by two loxPs.