Akt1 and Akt2 promote peripheral B-cell maturation and survival

被引：77

作者：

Calamito, Marco ^{[1
]}

Juntilla, Marisa M. ^{[1
]}

Thomas, Matthew ^{[1
]}

Northrup, Daniel L. ^{[1
]}

Rathmell, Jeffrey ^{[2
]}

Birnbaum, Morris J. ^{[3
,4
]}

Koretzky, Gary ^{[1
,3
,5
]}

Allman, David ^{[1
]}

机构：

[1] Univ Penn, Dept Pathol & Lab Med, Sch Med, Philadelphia, PA 19104 USA

[2] Duke Univ, Dept Pharmacol & Canc Biol, Durham, NC USA

[3] Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA

[4] Univ Penn, Sch Med, Dept Cell & Dev Biol, Philadelphia, PA 19104 USA

[5] Univ Penn, Sch Med, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA

来源：

BLOOD | 2010年 / 115卷 / 20期

关键词：

PHOSPHATIDYLINOSITOL; 3-KINASE; RECEPTOR SIGNALS; MUTANT MICE; BAFF-R; KINASE; LYMPHOCYTES; ACTIVATION; BCL-X(L); IMMUNOGLOBULIN; P110-DELTA;

D O I：

10.1182/blood-2009-09-241638

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Although the 3 isoforms of Akt regulate cell growth, proliferation, and survival in a wide variety of cell types, their role in B-cell development is unknown. We assessed B-cell maturation in the bone marrow (BM) and periphery in chimeras established with fetal liver progenitors lacking Akt1 and/or Akt2. We found that the generation of marginal zone (MZ) and B1 B cells, 2 key sources of antibacterial antibodies, was highly dependent on the combined expression of Akt1 and Akt2. In contrast, Akt1/2 deficiency did not negatively affect the generation of transitional or mature follicular B cells in the periphery or their precursors in the BM. How-ever, Akt1/2-deficient follicular B cells exhibited a profound survival defect when forced to compete against wild-type B cells in vivo. Altogether, these studies show that Akt signaling plays a key role in peripheral B-cell maturation and survival. (Blood. 2010; 115(20): 4043-4050)

引用

页码：4043 / 4050

页数：8

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