ATP11C is critical for the internalization of phosphatidylserine and differentiation of B lymphocytes.
Nat Immunol
; 12(5): 441-9, 2011 May.
Article
in En
| MEDLINE
| ID: mdl-21423173
ABSTRACT
Subcompartments of the plasma membrane are believed to be critical for lymphocyte responses, but few genetic tools are available to test their function. Here we describe a previously unknown X-linked B cell-deficiency syndrome in mice caused by mutations in Atp11c, which encodes a member of the P4 ATPase family thought to serve as 'flippases' that concentrate aminophospholipids in the cytoplasmic leaflet of cell membranes. Defective ATP11C resulted in a lower rate of phosphatidylserine translocation in pro-B cells and much lower pre-B cell and B cell numbers despite expression of pre-rearranged immunoglobulin transgenes or enforced expression of the prosurvival protein Bcl-2 to prevent apoptosis and abolished pre-B cell population expansion in response to a transgene encoding interleukin 7. The only other abnormalities we noted were anemia, hyperbilirubinemia and hepatocellular carcinoma. Our results identify an intimate connection between phospholipid transport and B lymphocyte function.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Phosphoserine
/
B-Lymphocytes
/
Cell Differentiation
/
Adenosine Triphosphatases
/
Endocytosis
Limits:
Animals
Language:
En
Journal:
Nat Immunol
Journal subject:
ALERGIA E IMUNOLOGIA
Year:
2011
Document type:
Article
Affiliation country:
Australia