The Journal of Immunology,
Год журнала:
2023,
Номер
211(9), С. 1308 - 1319
Опубликована: Сен. 18, 2023
Gain-of-function
polymorphisms
in
the
transcription
factor
IFN
regulatory
5
(IRF5)
are
associated
with
an
increased
risk
of
developing
systemic
lupus
erythematosus.
Global
homozygous
or
heterozygous
deficiency
IRF5
from
birth
confers
protection
many
mouse
models.
However,
less
is
known
about
effects
targeting
after
autoimmunity
has
already
developed.
This
important
point
to
clarify
when
considering
as
a
potential
therapeutic
target
lupus.
In
this
study,
we
demonstrate
that
genetic
reduction
expression
disease
initiation
reduces
severity
FcγRIIB-/-
Y-linked
autoimmune
accelerating
model.
Reduction
resulted
decrease
splenomegaly
and
lymphadenopathy
splenic
B
cell
activation
plasmablast
numbers.
Splenic
T
differentiation
were
also
impacted
demonstrated
by
increase
number
naive
CD4+
CD8+
cells
memory/effector
cells.
Although
serum
antinuclear
autoantibody
levels
not
altered,
led
decreased
immune
complex
deposition
complement
activation,
diminished
glomerular
interstitial
disease,
infiltrate
kidney.
Mechanistically,
myeloid
kidney
produced
inflammatory
cytokines
TLR7
TLR9
activation.
Overall,
during
active
process
sufficient
reduce
severity.
Our
data
support
consideration
suggest
approaches
erythematosus
may
need
impact
activity
both
systemically
organs.
British Journal of Dermatology,
Год журнала:
2024,
Номер
191(2), С. 164 - 176
Опубликована: Март 19, 2024
Pemphigus
vulgaris
(PV)
is
a
rare
autoimmune
bullous
disease
characterized
by
blistering
of
the
skin
and
mucosa
owing
to
presence
autoantibodies
against
desmosome
proteins
desmoglein
3
occasionally
in
conjunction
with
1.
Fundamental
research
into
pathogenesis
PV
has
revolutionized
its
treatment
outcome
rituximab,
B-cell-depleting
therapy.
The
critical
contribution
B
cells
pemphigus
well
accepted.
However,
exact
pathomechanism,
mechanisms
onset,
course
relapse
remain
unclear.
In
this
narrative
review,
we
provide
an
overview
fundamental
progress
that
unfolded
over
past
few
centuries
give
rise
current
emerging
therapies.
Furthermore,
summarize
multifaceted
roles
PV,
including
their
development,
maturation
antibody
activity.
Finally,
explored
how
these
various
aspects
B-cell
function
contribute
pave
way
for
innovative
therapeutic
interventions.
Biomolecules,
Год журнала:
2025,
Номер
15(1), С. 84 - 84
Опубликована: Янв. 8, 2025
Traditionally,
research
on
the
adaptive
immune
system
has
focused
protein
antigens,
but
emerging
evidence
underscored
essential
role
of
lipid
antigens
in
modulation.
Lipid
are
presented
by
CD1
molecules
and
activate
invariant
natural
killer
T
(iNKT)
cells
group
1
CD1-restricted
cells,
whereby
they
impact
responses
to
pathogens
tumors.
Recent
advances
mass
spectrometry,
imaging
techniques,
lipidomics
have
revolutionized
identification
characterization
enhanced
our
understanding
their
structural
diversity
functional
significance.
These
advancements
paved
way
for
lipid-based
vaccines
immunotherapies
through
application
nanoparticles
synthetic
designed
boost
against
cancers
infectious
diseases.
trafficking,
molecule
interactions,
system's
response
yet
be
completely
understood,
particularly
context
autoimmunity
microbial
infections.
In
years
come,
continued
efforts
needed
uncover
its
underlying
biological
mechanisms
exploit
full
potential
therapies
directed
antigens.
Frontiers in Immunology,
Год журнала:
2025,
Номер
15
Опубликована: Янв. 10, 2025
While
durable
antibody
responses
from
long-lived
plasma
cell
(LLPC)
populations
are
important
for
protection
against
pathogens,
LLPC
may
be
harmful
if
they
produce
antibodies
self-proteins
or
self-nuclear
antigens
as
occurs
in
autoimmune
diseases
such
systemic
lupus
erythematosus
(SLE).
Thus,
the
elimination
of
autoreactive
improve
treatment
antibody-driven
diseases.
However,
remain
a
challenging
therapeutic
target.
Here,
we
compare
matched
bone
marrow
(BM)
and
peripheral
blood
(PBL)
(PC)
compartments
SLE
healthy
donors
(HD).
We
show
similar
distribution
CD138-
CD138+
PC,
including
putative
(CD19-
CD38+),
between
HD
BM.
For
both
HD,
PC
at
higher
frequency
BM
than
PBL.
Expression
Ki-67
associates
with
PBL
compartment
where
it
is
found
on
all
subsets
regardless
CD19
CD138
expression.
Transcriptomic
analysis
identifies
an
interferon
(IFN)
gene
signature
transitional
B
cells
BM,
but
surprisingly
also
derived
SLE.
phosphorylate
STAT1
response
to
type
I
IFN
stimulation
vitro,
decreased
fold
change
compared
those
bind
receptor-blocking
anifrolumab,
lesser
degree
circulating
cells.
Anti-nuclear
autoantibodies
(ANA)
supernatant
serum
patients.
Both
BM-derived
have
increased
survival
their
counterparts
when
treated
verdinexor.
In
summary,
these
findings
evidence
activation
The Journal of Experimental Medicine,
Год журнала:
2025,
Номер
222(5)
Опубликована: Фев. 20, 2025
Newly
generated
plasma
cells
in
secondary
lymphoid
organs
migrate
to
niches
the
bone
marrow,
wherein
they
survive
as
long-lived
(LLPCs).
Although
LLPCs
have
been
extensively
characterized,
it
is
still
unclear
what
key
determinant(s)
are
for
cell
longevity.
One
model
postulates
that
heterogeneity
established
at
induction
site,
thereby
instructing
their
Here,
we
found
that,
among
newly
IgG
cells,
integrin
β7hi
marks
predisposed
home
whereas
β7lo
remain
organs.
Mechanistically,
this
egress-prone
fraction
had
a
higher
expression
of
KLF2
transcription
factor,
loss
which
resulted
defective
egress
by
downregulating
S1PR1
and
CD11b.
Disruption
results
antibody
durability,
making
mice
more
susceptible
influenza
reinfection.
Thus,
migration
program
site
plays
critical
role
determining
durability.
Abstract
Malaria
is
caused
by
protozoan
parasites
in
the
genus
Plasmodium.
Over
time
individuals
slowly
develop
clinical
immunity
to
malaria,
but
this
process
occurs
at
variable
rates,
and
mechanism
of
protection
not
fully
understood.
We
have
recently
demonstrated
that
genetically
identical
C57BL/6N
mice,
gut
microbiota
composition
dramatically
impacts
quality
humoral
immune
response
Plasmodium
yoelii
subsequent
against
a
lethal
secondary
challenge
with
berghei
ANKA
mice.
Here,
we
utilize
identical,
microbiome–dependent
model
investigate
how
modulate
immunological
memory,
hypothesizing
microbiome
formation
functionality
memory.
In
support
hypothesis,
P.
hyperparasitemia–resistant
mice
exhibit
increased
ANKA–induced
experimental
cerebral
malaria
(ECM)
compared
hyperparasitemia–susceptible
Despite
differences
ECM,
yoelii–resistant
–susceptible
accumulate
similar
numbers
memory
B
cells
(MBCs)
T
cells.
Following
ANKA,
generated
more
rapid
germinal
center
reactions;
however,
had
titers
yoelii–
berghei–specific
antibodies.
contrast,
an
number
regulatory
which
may
dampen
immune-mediated
breakdown
blood–brain
barrier
susceptibility
berghei–induced
ECM.
These
findings
demonstrate
ability
shape
potential
enhance
resistance
severe
outcomes.
medRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2025,
Номер
unknown
Опубликована: Май 14, 2025
Abstract
Immunological
memory
is
a
defining
feature
of
immunity,
yet
surprisingly
there
no
consensus
on
how
to
quantitatively
describe
antibody
titers
wane
over
time.
A
major
problem
that
the
slow
waning
requires
collection
data
for
decades
post-infection
or
vaccination.
Our
analysis
largest
existing
dataset
shows
power-law
model
describes
better
than
other
frequently
used
models.
suggests:
(i)
Protective
levels
antibodies
many
vaccine/virus
antigens
may
be
maintained
longer
previously
estimated.
(ii)
The
rate
protein
toxoid
vaccines
such
as
tetanus
similar
those
elicited
by
live
virus
infections.
(iii)
long-term
can
estimated
from
much
shorter
time-frame
about
1-3
years
following
immunization,
suggesting
using
could
allow
rapid
estimation
immunity
new
vaccines.
Durable
serological
memory
following
vaccination
is
critically
dependent
on
the
production
and
survival
of
long-lived
plasma
cells
(LLPCs).
Yet,
factors
that
control
LLPC
specification
remain
poorly
resolved.
Using
intravital
two-photon
imaging,
we
find
in
contrast
to
most
(PCs)
bone
marrow
(BM),
LLPCs
are
uniquely
sessile
organized
into
clusters
APRIL,
an
important
factor.
deep,
bulk
RNA
sequencing,
surface
protein
flow-based
phenotyping,
express
a
unique
transcriptome
phenotype
compared
PCs,
fine-tuning
expression
key
cell
molecules,
CD93,
CD81,
CXCR4,
CD326,
CD44,
CD48,
for
adhesion
homing.
Conditional
deletion
Cxcr4
PCs
immunization
leads
rapid
mobilization
from
BM,
reduced
antigen-specific
ultimately
accelerated
decay
antibody
titer.
In
naïve
mice,
endogenous
BCR
repertoire
exhibits
diversity,
somatic
mutations,
increased
public
clones
IgM
isotypes,
particularly
young
suggesting
non-random.
As
mice
age,
BM
PC
compartment
becomes
enriched
LLPCs,
which
may
outcompete
limit
entry
new
niche
pool.
Frontiers in Immunology,
Год журнала:
2023,
Номер
14
Опубликована: Дек. 11, 2023
Memory
B
cells
and
antibody-secreting
are
the
two
prime
effector
cell
populations
that
drive
infection-
vaccine-induced
long-term
antibody-mediated
immunity.
The
immunity
mostly
relies
on
formation
of
specialized
structures
within
secondary
lymphoid
organs,
called
germinal
centers
(GCs),
facilitate
interactions
between
cells,
T
antigen-presenting
cells.
Antigen-activated
may
proliferate
differentiate
into
GC-independent
plasmablasts
memory
or
GC
undergo
proliferation
coupled
to
somatic
hypermutation
their
immunoglobulin
genes
for
antibody
affinity
maturation.
Subsequently,
mature
GC-dependent
plasma
Here,
we
review
how
NFκB
signaling
system
controls
generation
plasmablasts/plasma
We
also
identify
discuss
some
important
unanswered
questions
in
this
connection.
Durable
serological
memory
following
vaccination
is
critically
dependent
on
the
production
and
survival
of
long-lived
plasma
cells
(LLPCs).
Yet,
factors
that
control
LLPC
specification
remain
poorly
resolved.
Using
intravital
two-photon
imaging,
we
find
in
contrast
to
most
(PCs)
bone
marrow
(BM),
LLPCs
are
uniquely
sessile
organized
into
clusters
APRIL,
an
important
factor.
deep,
bulk
RNA
sequencing,
surface
protein
flow-based
phenotyping,
express
a
unique
transcriptome
phenotype
compared
PCs,
fine-tuning
expression
key
cell
molecules,
CD93,
CD81,
CXCR4,
CD326,
CD44,
CD48,
for
adhesion
homing.
Conditional
deletion
Cxcr4
PCs
immunization
leads
rapid
mobilization
from
BM,
reduced
antigen-specific
ultimately
accelerated
decay
antibody
titer.
In
naïve
mice,
endogenous
BCR
repertoire
exhibits
diversity,
somatic
mutations,
increased
public
clones
IgM
isotypes,
particularly
young
suggesting
non-random.
As
mice
age,
BM
PC
compartment
becomes
enriched
LLPCs,
which
may
outcompete
limit
entry
new
niche
pool.