Page 105 - 80_01

Class
I
phosphoinositide
3-­-kinases
in
immunity…

Class
IA
catalytic
Normal
development;
n.d.
(63)

Pik3ca

normal
responses
in
vitro

p110a
CD2Cre
and
in
vivo

(lymphocyte

specific
deletion)

n.d.
(63)

Normal

Pik3cb

p110ß
CD2Cre

(lymphocyte

specific
deletion)

No
alterations
detected
(64,65)

Impaired
B
cell

homeostasis
activation
and
Impaired
Tfh,
ICOS
signaling

(74)

Pik3cd

function

p110d-­-/-­-

Impaired
T
cell
activation
(66-­-68).

and
function,
inflammatory
(63)

p110d
CD4Cre
(T
Impaired
B
cell
activation
bowel
disease

cell
specific
and
function,
enhanced
IgE

deletion)
levels
n.d.

p110dD910A/D910A

p110d
or
p110d
signal

tonic
BCR
signaling,
B
cell

p110a
CD2Cre
development
and
survival;

lymphocyte
specific
p110d
essential
in
agonist

deletion;
BCR
signaling

(24,69,75-­-78).

p110dD910A/D910A

(70,79)

Altered
thymocyte

Class
IB
catalytic
B
cells
normal
development,
impaired
or

Pik3cg

normal
activation,
impaired

p110?-­-/-­-

Similar
to
p110d-­-/-­-
or
migration

p110dD910A/D910A

Blocked
pre-­-TCR
signal,

p110?-­-/-­-
p110d-­-/-­-

severe
T
cell
high
thymocyte

p110?-­-/-­-
apoptosis,
severe
T
cell

p110dD910A/D910A
lymphopenia,
Th2-­-skewed

responses,
high
IgE
levels

The
study
of
the
effect
of
losing
p110a
or
p110ß
on
lymphocyte

development
and
function
has
been
impaired
by
the
embryonic
or
early
lethality

after
birth
of
null
(p110a-­-/-­-
and
p110ß-­-/-­-)
or
knock-­-in
kinase-­-dead
(p110aD933A
and

p110ßK805R)
mutant
mice
(reviewed
in
(5)).
Lymphocyte-­-specific
conditional

deletion
of
p110a
or
p110ß
in
floxed
p110a/CD2-­-Cre
or
floxed
p110ß/CD2-­-Cre

mice
showed
no
defect
in
B
lymphocytes
(63).
In
contrast,
p110d-­-/-­-
(64,65)
and

p110dD910A
mice
are
viable
and
have
defects
in
B
cell
antigen
receptor
(BCR)-­-
induced
activation
(63,66).

103