bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2023,
Volume and Issue:
unknown
Published: Oct. 6, 2023
Abstract
Bruton’s
tyrosine
kinase
(BTK)
is
a
major
drug
target
in
immune
cells.
The
membrane-binding
pleckstrin-homology
and
tec-homology
(PH–TH)
domains
of
BTK
are
required
for
signaling.
In
vitro,
dimerization
the
PH–TH
module
strongly
stimulates
activity.
Whether
dimerizes
cells
via
module,
whether
this
necessary
signaling,
unknown.
To
address
question,
we
developed
high-throughput
mutagenesis
assays
function
B
T
We
measured
fitness
costs
thousands
point
mutations
domain,
allowing
us
to
assess
activity
function.
Ramos
find
that
neither
nor
Instead,
cells,
signaling
enhanced
by
increase
membrane
adsorption,
even
at
cost
reduced
dimerization.
contrast,
Jurkat
depends
on
both
Evolutionary
analysis
shows
proteins
fish
lower
organisms,
like
all
Tec
kinases
other
than
BTK,
lack
but
have
active
domains.
Thus,
not
intrinsically
Tec-kinase
activity,
special
feature
evolved
exert
stricter
regulatory
control
as
adaptive
systems
gained
increased
complexity.
Fish & Shellfish Immunology,
Journal Year:
2024,
Volume and Issue:
148, P. 109523 - 109523
Published: March 24, 2024
Melanin
and
the
process
of
melanin
synthesis
or
melanogenesis
have
central
roles
in
immune
system
insects,
production
melanin-synthesizing
enzymes
from
their
haemocytes
may
be
induced
following
activation
through
danger
signals.
Melanin-containing
macrophage-like
cells
been
extensively
studied
amphibians
they
are
also
present
reptiles.
In
fish,
melano-macrophages
especially
recognized
with
respect
to
melano-macrophage
centres
(MMCs),
hypothesized
analogues
germinal
secondary
lymphoid
organs
mammals
some
birds.
Melano-macrophages
addition
several
inflammatory
conditions,
particular
melanised
focal
changes,
black
spots,
musculature
farmed
Atlantic
salmon,
Salmo
salar.
Melanins
complex
compounds
that
divided
into
different
forms
which
all
ability
absorb
scatter
light.
Other
functions
include
quenching
free
radicals
a
direct
effect
on
system.
According
common
view
held
pigment
cell
community,
vertebrate
melanosome
formation
only
occur
ectodermal
origin.
However,
abundant
information
suggests
myeloid
ectothermic
vertebrates
classified
as
melanocytes.
Here,
we
discuss
these
opposing
views
review
relevant
literature.
Finally,
current
status
research
concerning
muscle
changes
represent
most
severe
quality
problem
Norwegian
salmon
production,
but
other
diseases
where
play
important
roles.
Fish & Shellfish Immunology,
Journal Year:
2023,
Volume and Issue:
144, P. 109280 - 109280
Published: Dec. 10, 2023
In
the
present
study,
we
review
structure
and
function
of
fish
spleen
with
special
emphasis
on
its
condition
in
Elasmobranchs,
Teleosts
Lungfish.
Apart
from
amount
splenic
lymphoid
tissue,
histological
organization
organ
ensures
existence
areas
involved
antigen
trapping,
ellipsoids,
exhibit
numerous
melano-macrophages
which
appear
isolated
or
forming
so-called
melano-macrophage
centres.
An
extensive
discussion
functional
significance
these
centres
conclude
that
they
are
mere
accumulations
macrophages
consequence
tissue
homeostasis
rather
than
primitive
germinal
centres,
as
proposed
by
some
authors.
Fish & Shellfish Immunology,
Journal Year:
2024,
Volume and Issue:
145, P. 109358 - 109358
Published: Jan. 3, 2024
The
spleen
is
a
conserved
secondary
lymphoid
organ
that
emerged
in
parallel
to
adaptive
immunity
early
jawed
vertebrates.
Recent
studies
have
applied
single
cell
transcriptomics
reveal
the
cellular
composition
of
several
species,
cataloguing
diverse
immune
types
and
subpopulations.
In
this
study,
51,119
nuclei
transcriptomes
were
comprehensively
investigated
commercially
important
teleost
Atlantic
salmon
(Salmo
salar
L.),
contrasting
control
animals
with
those
challenged
bacterial
pathogen
Aeromonas
salmonicida.
We
identified
clusters
representing
expected
major
types,
namely
T
cells,
B
natural
killer-like
granulocytes,
mononuclear
phagocytes,
endothelial
mesenchymal
erythrocytes
thrombocytes.
discovered
heterogeneity
within
lineages,
providing
evidence
for
resident
macrophages
melanomacrophages,
infiltrating
monocytes,
candidate
dendritic
subpopulations,
cells
at
distinct
stages
differentiation,
including
plasma
an
igt
+
subset.
provide
twelve
subsets,
cd4+
helper
regulatory
one
cd8+
subset,
three
γδT
populations
double
negative
cd4
cd8.
number
genes
showing
differential
expression
during
infection
was
highly
variable
across
largest
changes
observed
followed
by
resting
mature
cells.
Our
analysis
provides
local
inflammatory
response
alongside
maturation
spleen,
upregulation
ccr9
consistent
recruitment
gut
deal
infection.
Overall,
study
new
cell-resolved
perspective
actions
highlighting
extensive
hidden
bulk
transcriptomics.
further
large
catalogue
cell-specific
marker
can
be
leveraged
explore
function
structural
organization
salmonid
system.
The Journal of Experimental Medicine,
Journal Year:
2025,
Volume and Issue:
222(6)
Published: March 4, 2025
Lymph
nodes
and
other
secondary
lymphoid
organs
play
critical
roles
in
immune
surveillance
activation
mammals,
but
the
deep
internal
locations
of
these
make
it
challenging
to
image
study
them
living
animals.
Here,
we
describe
a
previously
uncharacterized
external
organ
zebrafish
ideally
suited
for
studying
cell
dynamics
vivo,
axillary
(ALO).
This
small,
translucent
has
an
outer
cortex
teeming
with
cells,
inner
medulla
mesh-like
network
fibroblastic
reticular
cells
along
which
migrate,
lymphatic
vessels
draining
large
adjacent
lymph
sac.
Noninvasive
high-resolution
imaging
transgenically
marked
can
be
carried
out
ALOs
animals,
are
readily
accessible
treatment.
newly
discovered
tissue
provides
superb
model
dynamic
live
their
interaction
pathogens
surrounding
tissues,
including
blood
vessels.
The Journal of Immunology,
Journal Year:
2025,
Volume and Issue:
unknown
Published: May 15, 2025
Abstract
Secondary
lymphoid
organs
(SLOs)
provide
a
structured
environment
to
facilitate
interactions
between
low
frequency
antigen-specific
B
and
T
cells
as
well
cognate
antigen
displayed
by
presenting
(APCs),
resulting
in
the
initiation
of
effective
adaptive
immune
responses.
The
spleen
is
most
evolutionary
ancient
SLO,
emerging
concurrently
with
immunity
an
early
jawed
vertebrate
ancestor.
In
mammals,
immunoprotective
role
complemented
that
other
SLOs,
notably
network
draining
lymph
nodes
gut-associated
tissue
(GALT)
screen
for
infections
throughout
host.
However,
are
only
present
endothermic
vertebrates
(ie,
mammals
possibly
some
birds),
so
it
unclear
how
majority
species
maintain
robust
surveillance
their
entire
body
produce
timely
efficacious
antibody
While
investigating
responses
nurse
shark,
cartilaginous
fish
(Chondrichthyes)
which
last
shared
common
ancestor
∼450
million
yr
ago,
we
discovered
pancreas
contains
cell
follicles
spatially
distinct
from
exocrine
endocrine
pancreas.
Furthermore,
these
“pancreatic
follicles”
exhibit
many
hallmarks
selection
previously
identified
shark
spleen.
Our
results
also
demonstrate
antibodies
produced
within
following
immunization.
study
supports
designation
SLO
provides
insight
into
may
function
absence
nodes.
Science Signaling,
Journal Year:
2025,
Volume and Issue:
18(869)
Published: Jan. 14, 2025
Bruton’s
tyrosine
kinase
(BTK)
is
a
major
drug
target
in
immune
cells.
The
membrane-binding
pleckstrin
homology
and
tec
(PH-TH)
domains
of
BTK
are
required
for
signaling.
Dimerization
the
PH-TH
module
strongly
stimulates
activity
vitro.
Here,
we
investigated
whether
dimerizes
cells
using
this
dimerization
necessary
To
address
question,
developed
high-throughput
mutagenesis
assays
function
Ramos
B
Jurkat
T
We
measured
fitness
costs
thousands
point
mutations
domain
to
assess
were
function.
In
cells,
found
that
neither
nor
was
Instead,
signaling
enhanced
by
increased
membrane
adsorption,
even
at
cost
reduced
dimerization.
contrast,
depended
on
both
activity.
Evolutionary
analysis
indicated
proteins
organisms
evolved
before
divergence
ray-finned
fishes
lacked
but
had
active
domains,
similar
other
Tec
family
kinases.
Thus,
distinct
feature
exert
stricter
regulatory
control
as
adaptive
systems
gained
complexity.
Cells,
Journal Year:
2025,
Volume and Issue:
14(3), P. 223 - 223
Published: Feb. 5, 2025
Determining
an
individual’s
humoral
immune
reactivity
to
a
pathogen,
autoantigen,
or
environmental
agent
is
traditionally
accomplished
through
the
assessment
of
specific
antibody
levels
in
blood.
However,
many
instances,
titers
antibodies
decline
over
time
and
thus
do
not
faithfully
reveal
prior
antigen
exposure
establishment
immunological
memory.
To
estimate
competence,
it
therefore
necessary
assess
functional
B
cell
Here,
we
describe
novel
ELISPOT
FluoroSpot
assays
(collectively
referred
as
ImmunoSpot)
that
can
be
rapidly
developed
validated
characterize
memory
(Bmem)
repertoire
for
any
desired
ex
vivo
at
single-cell
resolution.
Moreover,
multiplexed
variants
assay
enable
high-throughput
testing
antigen-specific
cells
secreting
distinct
classes
and/or
IgG
subclasses,
with
minimal
material
requirements.
ImmunoSpot
also
measurement
affinity
distributions
within
Bmem
compartment
permit
cross-reactivity
measurements
provide
insights
into
established
against
future
pathogen
variants.
Collectively,
ImmunoSpot®
system
presented
here
highly
reproducible,
readily
regulated
tests.
The
newly
gained
ability
monitor
should
catalyze
more
comprehensive
understanding
immunity
health
disease.