期刊
EUROPEAN JOURNAL OF IMMUNOLOGY
卷 42, 期 12, 页码 3381-3393出版社
WILEY
DOI: 10.1002/eji.201242397
关键词
B cell; NFAT; PKB; Akt; SDF1a; STAT5
类别
资金
- Deutsche Forschungsgemeinschaft [FOR303/2, BO1054/2-1, SFB854-TP9]
Ligation of the BCR induces a complex signaling network that involves activation of Akt, a family of serine/threonine protein kinases associated with B-cell development, proliferation, and tumor formation. Here, we analyzed the effect of enhanced Akt1 signals on B-cell maturation and function. Unexpectedly, we found that peripheral B cells overexpressing Akt1 were less responsive to BCR stimuli. This correlated with a decrease in Ca2+-mobilization and proliferation, in an impaired activation of Erk1/2 and mammalian target of rapamycin (mTOR) kinases and poor mobilization of NFATc1 and NF-?B/p65 factors. In contrast, activation of STAT5 and migration of B cells toward the chemokine SDF1a was found to be enhanced. Akt1 Tg mice showed an altered maturation of peritoneal and splenic B1 B cells and an enhanced production of IgG1 and IgG3 upon immunization with the T-cell independent Ag TNP-Ficoll. Furthermore, mice homo-zygous for Tg Akt1 showed a severe block in the maturation of B-cell precursors in BM and a strong enrichment of plasma cells in spleen. Altogether, our data reveal that enhanced Akt1 signals modify BCR signaling strength and, thereby, B-cell development and effector function.
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