Constitutive Akt1 signals attenuate B-cell receptor signaling and proliferation, but enhance B-cell migration and effector function
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. Unexp...
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| Main Authors: | , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
18 December 2012
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| In: |
European journal of immunology
Year: 2012, Volume: 42, Issue: 12, Pages: 3381-3393 |
| ISSN: | 1521-4141 |
| DOI: | 10.1002/eji.201242397 |
| Online Access: | Verlag, Volltext: http://dx.doi.org/10.1002/eji.201242397 Verlag, Volltext: https://www.onlinelibrary.wiley.com/doi/abs/10.1002/eji.201242397 
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| Author Notes: | Mandy Pierau, Shin-Young Na, Narasimhulu Simma, Theresa Lowinus, Alexander Marx, Burkhart Schraven and Ursula H. Bommhardt |
| Summary: | 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-κB/p65 factors. In contrast, activation of STAT5 and migration of B cells toward the chemokine SDF1α 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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| Item Description: | Gesehen am 05.11.2018 |
| Physical Description: | Online Resource |
| ISSN: | 1521-4141 |
| DOI: | 10.1002/eji.201242397 |