Essential role of Stat5 for IL-5-dependent IgH switch recombination in mouse B cells

IL-5 stimulation of CD38-activated murine splenic B cells induces mu-gammal CSR at the DNA level leading to a high level of IgG1 production. Further a ddition of IL-4 in the system enhances IL-5-dependent mu-gammal CSR. Althou gh some of the postreceptor signaling events initiated by IL-5 in activated B cells have been characterized, the involvement of Stat in IL-5 signaling has not been thoroughly evaluated. In this study, we examined the activati on of Stat5 and activation-induced cytidine deaminase (AID) in CD38-activat ed murine splenic B cells by IL-5. The role of Stat5a and Stat5b in IL-5-in duced mu-gammal CSR and also IgG1 and IgM production was documented, as IL- 5 does not act on CD38-stimulated splenic B cells from Stat5a(-/-) and Stat 5b(-/-) mice. Expression levels of CD38-induced germline gamma1 transcripts and AID in Stat5a-/- and Stat5b-/- B cells upon IL-5 stimulation were comp arable to those of wild-type B cells. The impaired mu-gammal CSR by Stat5b- /- B cells, but not by Stat5a-/- B cells, was rescued in part by IL-4, as t he addition of IL-4 to the culture of CD38- and IL-5-stimulated B cells ind uced mu-gammal CSR leading to IgG1 production. Analysis of cell division cy cle number of wild-type B cells revealed that mu-gammal CSR was observed af ter five or six cell divisions. Stat5a(-/-) and Stat5b(-/-) B cells showed similar cell division cycles, but they did not undergo mu-gammal CSR. Our d ata support the notion that both Stat5a and Stat5b are essential for IL-5-d ependent mu-gammal CSR and Ig secretion; however, their major target may no t be AID. Stat5a and Stat5b are not redundant, but rather are at least part ially distinctive in their function.