Constitutive Akt1 signals attenuate B-cell receptor signaling and proliferation, but enhance B-cell migration and effector function

• Verfasst von: Pierau, Mandy [VerfasserIn]
• Verfasst von: Marx, Alexander [VerfasserIn]
• Titel: Constitutive Akt1 signals attenuate B-cell receptor signaling and proliferation, but enhance B-cell migration and effector function
• Verf.angabe: Mandy Pierau, Shin-Young Na, Narasimhulu Simma, Theresa Lowinus, Alexander Marx, Burkhart Schraven and Ursula H. Bommhardt
• E-Jahr: 2012
• Jahr: 18 December 2012
• Umfang: 13 S.
• Fussnoten: Gesehen am 05.11.2018
• Titel Quelle: Enthalten in: European journal of immunology
• Ort Quelle: Weinheim : Wiley-VCH, 1971
• Jahr Quelle: 2012
• Band/Heft Quelle: 42(2012), 12, Seite 3381-3393
• ISSN Quelle: 1521-4141
• DOI: doi:10.1002/eji.201242397
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: B cell
• Sach-SW: NFAT
• Sach-SW: PKB/Akt
• Sach-SW: SDF1α
• Sach-SW: STAT5
• K10plus-PPN: 1582583803

Abstract

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.