B Cell Activation and Differentiation Flashcards
what is phase 4 of b cell activation
just searchign, just going around body trying to find infection
what is phase 5 of b-cell activation
find infection
what is phase 6 of b cell activation
attacking infection
describe phase 6 of b cell activation
differentiation to antibody-secreting plasma cells and memory b cells in secondary lymphoid tissue
for the majority of b cell differentiation and expansion need the help of
t cell
naive b cell have lower amounts of
IgM on surface than IgD
mature naive B cell will enter
circulation
once b cell going through tissue it will find
is epitope
b cell soluble vs. on the b cell membrane
won’t be soluble until you’ve encountered pathogen
IgM vs. IgD decision is made at what level
RNA level ,made before pt is sick
somatic hypermutation
nothing but fine tuning the antibodies
making IgM stronger binding to whatever the thing is -so mutates until it binds better. make antibody better
memory cells will express what on surface
IgG
after mature b cell sees pathogen it becomes
activated B cell
transmembrane receptors convert extracellular signal into
intracellular biochemical events
what is the transmembrane receptor we are talking about
BCR
what is extracellular signal
antigen
inracellular signal propagation is mediated by
large multiprotein signaling complexes
activation of some receptors generate
small molecule second messengers
BCR consist of variable antigen-binding chains associated with
invariant chains that carry out the signaling function of receptor
invariant
Ig alpha dn Ig beta
what are the invariant chains
alpha and beta
Antigen recognition by the BCR and its co-receptors leads to phosphorylation of
ITAMs by Src-family kinases.
The logic of BCR signaling is similar to that of
what is the difference
TCR signaling
but some of the signaling components are specific to B cells.
Syk is a
tyrosine kinase
Phosphorylated ITAMs recruit and activate the
tyrosine kinase Syk
what does Syk do
phosphorylates scaffold proteins that recruit the phospholipase PLC-.
invariant are associated with antibody and altogether we call it the
BCR
Igbeta and IGalpha are critical b/c they have
cytoplasmic side - that is where you put phosphate to get things going
cross linking
receptors need to cross link when they find antigen
what happens to b cell receptor when they find antigen
cross linking
once there is cross linking, it will get you to
cluster antibodies on surface of cell
put phosphate on tyrosine residue what type of enzyme
kinase
Blk, Fyn, Lyn are
the key tyrosine kianses that do initial phosphorylation
what is key mediator for the b cell activation process
Syk
ITAM stand for
Immunoreceptor Tyrosine-based Activation Motifs
ITAMS are
particular part withing Igbet and Igalpha that will get phosphorylated
the initial phosphorylations initiate what to join
Syk
list steps in BCR signaling
cross linking
Src family kinases (Blk,Fyn,Lyn) are activated
ITAMs on Igα and Igβ are phosphorylated
Syk is recruited to phosphorylated ITAMs and activated
the actual onees that do ITAM phosphorylation are
Blk, Fyn, Lyn
now that ITAM is phosphorylated, recruit
Syk
what is the ultimate step in the BCR signaling process
transcrition factors - ultimately want to change the DNA and what is expressed. want to go to gene and turn it off or on
main TF for BCR signaling
NF-kappaB, NFAT, AP-1
after activate src kinases
phosphorylate ITAm
after hposphorylate ITAM
recruite & ativate Syk
after recruit and activate Syk, activate
activate PLCgamma
what are the key second messengers
DAG, IP3, Calcium
PLC gamma creates
DAG & IP3 (second messangers)
after DAG activate
kinases
after IP3 activate
Calcium
ultimately second messangers will turn on
TF: NF kappa beta, AP-1 and NFAT
list the steps of secondary lymphoid organs and circulation (basically start with mature b cell and go from there
Mature B cell: enters circulation and binds specific antigen, has IgM and IgG on surface → antigen-activated B lymphoblast, alternative splicing to secrete lg, iostype switching, somatic hypermutation → antibody secreting plasma cell IgM or IgG is secreted OR memory cell
draw out 2nd messenger chain
pg 11
CD19
it’s in all B cells
all B cells will express what molecule
CD19
what is CR2
complement receptor 2 - it is part of b-cell co-receptor
what does CR stand for
complement receptor
what is part of b cell co-receptor
CD19, CR2
CR2 binds directly with
complement - binds C3d on bacterial cell
c3d s another fragment of C3; in add’n to c3b you will have c3b
CD19 has ITAMs, describe what else it does
it is part of b-cell co-receptor
it is phosphorylated by BCR kinases
it is involved in positive signaling
signals from BCR and co-receptor act
synergistically
C3d is fragment of
C3
CD19 is phosphorylated by
BCR associated kinases
soluble antigens will interact with
C3d
soluble antigen recognized by
BCR - antigen binding side
after CR2 recognizes C3d and then what happens
CD19 is phosphorylated
what is one of the important mechanisms for slowing down immune system
negative co-receptor function of FcgammaR
what is Fcgamma R
IgG receptor
if there is enough IgG in body that you have floating IgG attached to antigen, it probably means
you have enough IgG
IgG released, soluble version of antibody, that soluble version floating around encounters on surface of B cell what recepor
FcgammaR
when IgG finds FcgammaR what happens
makes complex with the actual BCR on the surface of the B cell, it triggers the negative response.
Ig alpha and Ig beta are activation ,in the Fcgamme R you have ITIM (versus ITAM) they are also immuno receptor but they are inhibition
when ITIM is phosphorylated what happens
it slows down the process of clonal expansion, etc. it doesn’t shut down the whole b cell ,but shuts down the active part of making more antibodies, etc.
What does TI stand for
thymus independent
what does TD stand for
thymus dependent
If you don’t knw if it is TI or TD assume it is
TD
why does TD require protein
MHC needed and that needs peptide
TI antigen
polymeric antigen - most often polysaccharide
describe TI antigen
low affinity IgM
no class switching
no memory cells
B1 cells are thymus
independent
the cells that make IgM only are called
plasmablast
when there is capsule from bac. and it is bound to BCR/antibody it is very important for all the antibodies to do
multivalent crosslinking
draw out process for creating trasmembrane IgM and secreted IgM
pg 20
the alternative splicing for transmembrane IgM vs. secreted IgM occurs after
antigen exposure
T helpers need to play a role in
T dependent antigens
