Deciphering the Human Germinal Center: A Review of Models to Study T–B Cell Interactions
European Journal of Immunology,
Год журнала:
2025,
Номер
55(2)
Опубликована: Фев. 1, 2025
Interactions
between
T-
and
B
cells
in
the
germinal
center
reaction
are
instrumental
for
initiation,
maintenance,
downregulation
of
human
adaptive
immune
response,
leading
to
production
antigen-specific
antibodies
long-lasting
immunological
memory.
Replicating
system
remains
challenging,
with
an
over-reliance
on
animal
models
limited
translational
accuracy.
There
is
increasing
need
new
tools
that
accurately
model
function.
This
review
evaluates
existing
2D
3D
vitro
ex
vivo
their
ability
reproduce
reaction,
a
particular
focus
B-cell
interaction.
We
conclude
although
current
able
replicate
certain
features
no
completely
complex
GC
process.
outline
challenges
recreating
fully
functional
suggest
future
directions
research
improve
models,
ultimately
bringing
us
closer
reproducing
lymph
node.
Язык: Английский
Initiation of primary T cell—B cell interactions and extrafollicular antibody responses in an organized microphysiological model of the human lymph node
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 15, 2025
ABSTRACT
Antibody
production
is
central
to
protection
against
new
pathogens
and
cancers,
as
well
certain
forms
of
autoimmunity.
Antibodies
often
originate
in
the
lymph
node
(LN),
specifically
at
extrafollicular
border
B
cell
follicles,
where
T
lymphocytes
physically
interact
drive
maturation
into
antibody-secreting
plasmablasts.
In
vitro
models
this
process
are
sorely
needed
predict
aspects
human
immune
response.
Microphysiological
systems
(MPSs)
offer
opportunity
approximate
lymphoid
environment,
but
so
far
have
focused
primarily
on
memory
recall
responses
antigens
previously
encountered
by
donor
cells.
To
date,
no
3D
culture
system
has
replicated
engagement
between
cells
(T—B
interaction)
that
leads
antibody
when
starting
with
naïve
Here,
we
developed
a
LN-MPS
model
early
T—B
interactions
built
from
primary,
encapsulated
within
collagen-based
matrix.
Within
MPS,
exhibited
CCL21-dependent
chemotaxis
chemokinesis
predicted.
Naïve
were
successfully
skewed
chip
an
follicular
helper
(pre-Tfh)
activated
state,
respectively,
co-culture
latter
led
CD38+
plasmablast
dependent
IgM.
These
required
differentiation
pre-Tfhs,
physical
cell-cell
contact,
sensitive
ratio
which
pre-Tfh
seeded
on-chip.
Dependence
was
greatest
1:5
T:B
ratio,
while
proliferation
signal
1:1
ratio.
Furthermore,
formation
established
We
envision
MPS
primary
lymphocyte
physiology
will
enable
mechanistic
analyses
humoral
immunity
vitro.
Язык: Английский
Boosting B cells in blood-derived organoids
Nature Materials,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 24, 2025
Язык: Английский
Boosting human immunology: harnessing the potential of immune organoids
EMBO Molecular Medicine,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 27, 2025
Язык: Английский
Functional organotypic human lymph node model with native immune cells benefits from fibroblastic reticular cell enrichment
Scientific Reports,
Год журнала:
2025,
Номер
15(1)
Опубликована: Апрель 10, 2025
Lymphoid
organ
function
depends
on
fibroblastic
reticular
cells
(FRCs),
the
non-hematopoietic
mesenchymal
stromal
that
crucially
support
immune
activity
in
human
lymph
nodes
(LNs).
The
vitro
study
of
immunology
requires
physiological
LN
models,
yet
inclusion
FRCs
current
models
is
lacking.
Here,
we
created
an
organotypic
hydrogel
model,
containing
native
from
tissue
and
ex
vivo
cultured
autologous
FRCs.
During
a
oneweek
culture
period,
enrichment
into
model
benefited
viability
all
cell
populations,
particularly
B
cells,
promoted
presence
certain
subsets
including
CD4+
naïve
T
unswitched
(US)
memory
cells.
enhanced
production
immune-related
cytokines
chemokines,
such
as
activating
factor
TNF
family
(BAFF),
CXC
motif
chemokine
ligand
12
(CXCL12),
CC
19
(CCL19)
interleukin-6
(IL-6).
Functionality
was
assessed
through
activation
by
CD3
stimulation
or
initiation
allogenic
reaction
with
different
maturation
statuses
monocyte-derived
dendritic
(moDCs).
Interestingly,
expansion
restricted
FRC-enriched
reflecting
intrinsic
characteristic
As
such,
this
highlights
influence
allows
opportunity
to
further
antigen-induced
responses,
e.g.
vaccine
immunotherapy
testing.
Язык: Английский
Vaccinology: Getting our modernization act together
The Journal of Experimental Medicine,
Год журнала:
2025,
Номер
222(5)
Опубликована: Апрель 22, 2025
Ofer
Levy,
Director,
Precision
Vaccines
Program
at
Boston
Children’s
Hospital,
reflects
on
implications
of
the
new
FDA
Modernization
Act
2.0
accelerating
drug
and
vaccine
discovery
development.
Язык: Английский
Ex vivorecapitulation of intramuscular mRNA vaccination with naïve and recall antigens using a human Lymphoid Follicle Chip platform
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2025,
Номер
unknown
Опубликована: Апрель 17, 2025
Abstract
Predicting
the
efficacy
and
toxicity
of
intramuscular
mRNA
vaccines
remains
challenging.
Here,
we
describe
an
ex
vivo
human
cell-based
model
that
replicates
immune
responses
to
lipid
nanoparticle
(LNP)-based
require
injection.
Vaccines
are
administered
into
a
biomimetic
muscle
module
containing
skeletal
myoblasts
antigen-presenting
cells
(APCs)
mimic
vaccination,
followed
by
transfer
APCs
soluble
factors
microfluidic
lymphoid
follicle
chip
(LF
Chip)
lymphatic
drainage.
Non-replicating
directly
induce
antigen
expression
in
APCs,
whereas
self-amplifying
cell-APC
contact
within
vaccination
module.
Transfer
LF
Chip
induces
expansion,
de
novo
antigen-specific
IgG
production
against
naïve
(rabies
virus
glycoprotein),
cytokine
release,
with
varying
depending
on
LNP
type.
Vaccination
chips
SARS-COV-2
Spike
recall
using
Moderna
Spikevax
vaccine
generates
neutralizing
antibodies
somatic
hypermutation.
This
platform
offers
all-human
alternative
for
evaluating
vaccine-induced
immunity,
potentially
obviating
need
non-human
primates
accelerating
development.
Язык: Английский
Vaccination as a Promising Approach in Cardiovascular Risk Mitigation: Are We Ready to Embrace a Vaccine Strategy?
Biomolecules,
Год журнала:
2024,
Номер
14(12), С. 1637 - 1637
Опубликована: Дек. 20, 2024
Cardiovascular
disease
(CVD)
remains
a
leading
global
health
concern,
with
atherosclerosis
being
its
principal
cause.
Standard
CVD
treatments
primarily
focus
on
mitigating
cardiovascular
(CV)
risk
factors
through
lifestyle
changes
and
cholesterol-lowering
therapies.
As
is
marked
by
chronic
arterial
inflammation,
the
innate
adaptive
immune
systems
play
vital
roles
in
progression,
either
exacerbating
or
alleviating
development.
This
intricate
interplay
positions
system
as
compelling
therapeutic
target.
Consequently,
immunomodulatory
strategies
have
gained
increasing
attention,
though
none
yet
reached
widespread
clinical
adoption.
Safety
concerns,
particularly
suppression
of
host
defenses,
remain
significant
barrier
to
application
anti-inflammatory
Recent
decades
revealed
role
responses
plaque-associated
autoantigens
atherogenesis,
opening
new
perspectives
for
targeted
immunological
interventions.
Preclinical
models
indicate
that
vaccines
targeting
specific
atherosclerosis-related
can
slow
progression
while
preserving
systemic
function.
In
this
context,
numerous
experimental
studies
advanced
understanding
vaccine
development
exploring
diverse
pathways.
Key
include
passive
immunization
using
naturally
occurring
immunoglobulin
G
(IgG)
antibodies
active
low-density
lipoprotein
cholesterol
(LDL-C)
apolipoproteins,
such
apolipoprotein
B100
(ApoB100)
CIII
(ApoCIII).
Other
approaches
involve
formulations
aimed
at
proteins
regulate
metabolism,
including
proprotein
convertase
subtilisin/kexin
type
9
(PCSK9),
cholesteryl
ester
transfer
protein
(CETP),
angiopoietin-like
3
(ANGPTL3).
Furthermore,
literature
highlights
potential
developing
non-lipid-related
vaccines,
key
targets
heat
shock
(HSPs),
interleukins
(ILs),
angiotensin
III
(Ang
III),
disintegrin
metalloproteinase
thrombospondin
motifs
7
(ADAMTS-7).
However,
translating
these
promising
findings
into
safe
effective
therapies
presents
substantial
challenges.
review
provides
critical
evaluation
current
anti-atherosclerotic
vaccination
strategies,
examines
their
proposed
mechanisms
action,
discusses
challenges
need
be
overcome
enable
translation.
Язык: Английский