An. Real. Acad. Farm. vol 80 nº 1 2014 - page 103

Class I phosphoinositide3-­‐kinases in immunity…
103
Class IAcatalytic
Pik3ca
p110
α
CD2Cre
(lymphocyte
specificdeletion)
Normal development;
normal responses
invitro
and
invivo
n.d.
(63)
Pik3cb
p110
β
CD2Cre
(lymphocyte
specificdeletion)
Normal
n.d.
(63)
Pik3cd
p110
δ
-­‐/-­‐
ImpairedBcell
homeostasis activationand
function
Noalterationsdetected
(64,65)
p110
δ
CD4Cre (T
cell specific
deletion)
ImpairedTfh, ICOS signaling (74)
p110
δ
D910A/D910A
ImpairedBcell activation
and function, enhanced IgE
levels
ImpairedTcell activation
and function, inflammatory
bowel disease
(66-­‐68).
p110
α
CD2Cre
lymphocyte specific
deletion;
p110
δ
D910A/D910A
p110
δ
orp110
δ
signal
tonicBCRsignaling, Bcell
development andsurvival;
p110
δ
essential inagonist
BCRsignaling
n.d.
(63)
Class IBcatalytic
Pik3cg
p110
γ
-­‐/-­‐
Bcellsnormal
Altered thymocyte
development, impairedor
normal activation, impaired
migration
(24,69,75-­‐78).
p110
γ
-­‐/-­‐
p110
δ
-­‐/-­‐
p110
γ
-­‐/-­‐
p110
δ
D910A/D910A
Similar top110
δ
-­‐/-­‐
or
p110
δ
D910A/D91 A
Blocked pre-­‐TCR signal,
severeTcell high thymocyte
apoptosis, severe T cell
lymphopenia,
Th2-­‐skewed
responses, high IgE levels
(70,79)
The study of the effect of losing p110
α
or p110
β
on lymphocyte
development and function has been impaired by the embryonic or early lethality
afterbirthof null (p110
α
-­‐/-­‐
andp110
β
-­‐/-­‐
) or knock-­‐inkinase-­‐dead (p110
α
D933A
and
p110
β
K805R
) mutant mice (reviewed in (5)). Lymphocyte-­‐specific conditional
deletion of p110
α
or p110
β
in floxed p110
α
/CD2-­‐Cre or floxed p110
β
/CD2-­‐Cre
mice showed no defect in B lymphocytes (63). In contrast, p110
δ
-­‐/-­‐
(64,65) and
p110
δ
D910A
mice are viable and have defects in B cell antigen receptor (BCR)-­‐
inducedactivation(63,66).
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