Page 104 - 80_01

José
María
Rojo,
Pilar
Portolés

derived
from
mutant
ES
cells
had
less
mature
B
cells
and
low
serum

immunoglobulins;
in
vitro
activation
of
B
cells
was
also
impaired
(57).
Mice
lacking

p85a
subunits
but
not
p55a
or
p50a
had
a
similar
phenotype;
both
phenotypes

were
very
similar
to
the
X-­-linked
immunodeficiency
due
to
Bruton
tyrosine
kinase

(Btk)
deficiency
(58).
No
immunological
defects
have
been
described
in
mice

lacking
p55a
or
p50a
subunits
(59).
Deletion
of
p85ß
produced
normal
B
cell

responses
(60).
Last,
the
absence
of
p85a
and/or
p85ß
reduced
basal,
PI3K

dependent
lymphocyte
motility
of
B
lymphocytes
(61).
There
is
no
data
concerning

the
effect
of
class
IB
regulatory
subunit
loss
in
lymphocyte
function,
data
in

neutrophils
indicate
impaired
cytokine-­-driven
motility
(62)
(summarized
in
Table

1).

Table
1.-­-
Effect
of
Class
I
PI3-­-K
subunit
mutations
and
defects
in
B
and
T
lymphocyte
phenotype

and
function.

Subunit
Phenotype,
B
lymphocyte
Phenotype,
T
lymphocyte
Other

(References)

Class
IA
regulatory

Pik3r1

pan-­-p85a-­-/-­-
(p85a-­-/-­-

Perinatal

,
p55a-­-/-­-,
p50a-­-/-­-)
Low
B
cell
number;
Impaired
motility
lethality

impaired
activation
and
(57,61).

p85a-­-/-­-
only
motility
Normal
development,
(60,61,71)..

Impaired
motility
reduced
motility;
enhanced

p55a-­-/-­-,
p50a-­-/-­-

response
in
vitro;
lower
T-­- (59).

Normal
dependent
secondary

Pik3r2

response

p85ß-­-/-­-

Normal
(61)

p85a-­-/-­-,
p55a-­-/-­-,
Impaired
motility

(61,72,73).

p50a-­-/-­-;

p85ß-­-/-­-,
Impaired
motility

Impaired
motility

Impaired
motility,
Th2,
Treg

Pik3r3

differentiation;
autoimmune

p55?-­-/-­-

n.d.
syndrome

Class
IB
regulatory

Pik3r5

n.d.
Neutrophil

p101-­-/-­-

n.d.

migration

impaired
(62)

Pik3r6

n.d.

p87/84

n.d.

n.d.

102