Essential Role of Stat5 for IL-5-Dependent IgH Switch Recombination in Mouse B Cells
In: The Journal of Immunology, Jg. 167 (2001-11-01), S. 5018-5026
Online
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Zugriff:
IL-5 stimulation of CD38-activated murine splenic B cells induces μ-γ1 CSR at the DNA level leading to a high level of IgG1 production. Further addition of IL-4 in the system enhances IL-5-dependent μ-γ1 CSR. Although 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 activation of Stat5 and activation-induced cytidine deaminase (AID) in CD38-activated murine splenic B cells by IL-5. The role of Stat5a and Stat5b in IL-5-induced μ-γ1 CSR and also IgG1 and IgM production was documented, as IL-5 does not act on CD38-stimulated splenic B cells from Stat5a−/− and Stat5b−/− mice. Expression levels of CD38-induced germline γ1 transcripts and AID in Stat5a−/− and Stat5b−/− B cells upon IL-5 stimulation were comparable to those of wild-type B cells. The impaired μ-γ1 CSR by Stat5b−/− B cells, but not by Stat5a−/− B cells, was rescued in part by IL-4, as the addition of IL-4 to the culture of CD38- and IL-5-stimulated B cells induced μ-γ1 CSR leading to IgG1 production. Analysis of cell division cycle number of wild-type B cells revealed that μ-γ1 CSR was observed after five or six cell divisions. Stat5a−/− and Stat5b−/− B cells showed similar cell division cycles, but they did not undergo μ-γ1 CSR. Our data support the notion that both Stat5a and Stat5b are essential for IL-5-dependent μ-γ1 CSR and Ig secretion; however, their major target may not be AID. Stat5a and Stat5b are not redundant, but rather are at least partially distinctive in their function.
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Essential Role of Stat5 for IL-5-Dependent IgH Switch Recombination in Mouse B Cells
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Autor/in / Beteiligte Person: | Iwamoto, Itsuo ; Kariyone, Ai ; Horikawa, Keisuke ; Takatsu, Kiyoshi ; Kaku, Hiroaki ; Yasue, T ; Nakajima, Hiroshi ; Davey, Helen W. ; Hennighausen, Lothar |
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Zeitschrift: | The Journal of Immunology, Jg. 167 (2001-11-01), S. 5018-5026 |
Veröffentlichung: | The American Association of Immunologists, 2001 |
Medientyp: | unknown |
ISSN: | 1550-6606 (print) ; 0022-1767 (print) |
DOI: | 10.4049/jimmunol.167.9.5018 |
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