JoséMaríaRojo, Pilar Portolés
102
derived from mutant ES cells had less mature B cells and low serum
immunoglobulins;
invitro
activationof Bcellswas also impaired(57).Mice lacking
p85
α
subunits but not p55
α
or p50
α
had a similar phenotype; both phenotypes
were very similar to theX-‐linked immunodeficiencydue toBruton tyrosine kinase
(Btk) deficiency (58). No immunological defects have been described in mice
lacking p55
α
or p50
α
subunits (59). Deletion of p85
β
produced normal B cell
responses (60). Last, the absence of p85
α
and/or p85
β
reduced basal, PI3K
dependent lymphocytemotilityof B lymphocytes (61). There isnodataconcerning
the effect of class IB regulatory subunit loss in lymphocyte function, data in
neutrophils indicate impaired cytokine-‐drivenmotility (62) (summarized inTable
1).
Table 1.-‐
Effect of Class I PI3-‐K subunit mutations and defects in B and T lymphocyte phenotype
and function.
Subunit
Phenotype, Blymphocyte Phenotype, Tlymphocyte
Other
(References)
Class IAregulatory
Pik3r1
pan-‐p85
α
-‐/-‐
(p85
α
-‐/-‐
, p55
α
-‐/-‐
, p50
α
-‐/-‐
)
LowBcell number;
impairedactivationand
motility
Impairedmotility
Perinatal
lethality
(57,61).
p85
α
-‐/-‐
only
Impairedmotility
Normal development,
reducedmotility; enhanced
response
invitro
; lowerT-‐
dependent secondary
response
(60,61,71)..
p55
α
-‐/-‐
, p50
α
-‐/-‐
Normal
Normal
(59).
Pik3r2
p85
β
-‐/-‐
Impairedmotility
Impairedmotility
(61)
p85
α
-‐/-‐
, p55
α
-‐/-‐
,
p50
α
-‐/-‐
; p85
β
-‐/-‐
,
Impairedmotility
Impairedmotility, Th2, Treg
differentiation; autoimmune
syndrome
(61,72,73).
Pik3r3
p55
γ
-‐/-‐
n.d.
n.d.
Class IBregulatory
Pik3r5
p101
-‐/-‐
n.d.
n.d.
Neutrophil
migration
impaired(62)
Pik3r6
p87/84
n.d.
n.d.
