B Cell Activation and Differentiation Flashcards by Rebecca Ruthberg

what is phase 4 of b cell activation

just searchign, just going around body trying to find infection

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what is phase 5 of b-cell activation

find infection

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what is phase 6 of b cell activation

attacking infection

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describe phase 6 of b cell activation

differentiation to antibody-secreting plasma cells and memory b cells in secondary lymphoid tissue

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for the majority of b cell differentiation and expansion need the help of

t cell

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naive b cell have lower amounts of

IgM on surface than IgD

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mature naive B cell will enter

circulation

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once b cell going through tissue it will find

is epitope

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b cell soluble vs. on the b cell membrane

won’t be soluble until you’ve encountered pathogen

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IgM vs. IgD decision is made at what level

RNA level ,made before pt is sick

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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

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memory cells will express what on surface

IgG

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after mature b cell sees pathogen it becomes

activated B cell

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transmembrane receptors convert extracellular signal into

intracellular biochemical events

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what is the transmembrane receptor we are talking about

BCR

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what is extracellular signal

antigen

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inracellular signal propagation is mediated by

large multiprotein signaling complexes

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activation of some receptors generate

small molecule second messengers

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BCR consist of variable antigen-binding chains associated with

invariant chains that carry out the signaling function of receptor

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invariant

Ig alpha dn Ig beta

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what are the invariant chains

alpha and beta

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Antigen recognition by the BCR and its co-receptors leads to phosphorylation of

ITAMs by Src-family kinases.

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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.

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Syk is a

tyrosine kinase

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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

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

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

B Cell Activation and Differentiation Flashcards

(83 cards)