Akt1 and Akt2 promote peripheral B-cell maturation and survival.
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. However, 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.
Calamito
Marco
M
Department of Pathology and Laboratory of Medicine, University of Pennsylvania School of Medicine, Philadelphia, USA.
Juntilla
Marisa M
MM
Thomas
Matthew
M
Northrup
Daniel L
DL
Rathmell
Jeffrey
J
Birnbaum
Morris J
MJ
Koretzky
Gary
G
Allman
David
D
D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology*; D019070:Cell Lineage; D002470:Cell Survival; D005434:Flow Cytometry; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction
D012333:RNA, Messenger; C514862:Akt1 protein, mouse; C494922:Akt2 protein, mouse; D051057:Proto-Oncogene Proteins c-akt