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).