B cells and how they get activated

Question 1

where do B cells develop?

Answer 1

in the bone marrow

Question 2

how do B cells get activated?

Answer 2

Mature B cells get activated in the spleen or lymph nodes by naked antigen through the B cell receptor

Question 3

what is naked antigen?

Answer 3

antigen that is not presented by MHC

Question 4

where are mature B cell found?

Answer 4

circulating through the body

Question 5

what can B cells do?

Answer 5

• secrete antibody
• can present antigen on MHCII to CD4 T cells
• Can “class switch”
• Can undergo “somatic hypermutation”
• Undergo clonal expansion
• Can differentiate into antobody producing plasma cells

Question 6

what is the initiat step in B cell activation?

Answer 6

By signalling through the B cell receptor

Question 7

what is the B cell receptor?

Answer 7

Antibody bound to the plasma membrane

Question 8

why is it important to know how and why B cells are activated?

Answer 8

• develop new cures for cancer: B cell malignancies (lymphoma and leukemia)
• Develop new treatments for autoimmune diseases
• Make new vaccines

Question 9

how are B cell activated through the BCR?

Answer 9

Activation of a cell surface receptor through ligand binding doesn’t always directly link to the cell’s response

Question 10

how does the activated BCR act?

Answer 10

The activated receptors can interact with a chain of other proteins within the cell that transmit the activation signal (signal transduction pathway)

Question 11

what are kinases?

Answer 11

enzymes that phosphorylate themselves and other proteins- phosphorylation can generate binding sites for other proteins to allow the signal to transmit along the chain

Question 12

what is the cellular messengering of BCR?

Answer 12

First messenger- antigen

Transmembrane B cell receptor (surface-bound immunoglobulin + Igalpha and Igbeta)

second messengers

Cascade

Functions

Question 13

what is the structure of a BCR?

Answer 13

Cell surface immunoglobulin + one each of invariant signalling proteins Igalpha and Igbeta

• disulfide-link to form a heterodimer between Igalpha and Igbeta

Question 14

what are the co-receptors of B cells?

Answer 14

CD21 and CD19

Question 15

what is the role of B cell co-receptors?

Answer 15

Decreases BCR signaling threshold by amplifying BCR signals

Allows B cells to respond to low levels of antigen

Question 16

what is CD21?

Answer 16

complement receptor 2- binds to the complement-coupled antigen
- antigen coupled to complement fragment

Question 17

what is CD19?

Answer 17

augments signalling through BCR + recruites PI3-Kinase (growth signal)

Question 18

what is the role of CD81?

Answer 18

trafficks CD19 to the cell surface

Question 19

how are BCR presented on the cell surface?

Answer 19

there are many BCRs on the surface of one cell and they can move around the membrane on lipid rafts

Question 20

what is BCR receptor clustering?

Answer 20

the BCR are on lipid rafts. This allows them to move around the cell membrane and means the signal can agrigate to one region of the BCR to get a much stronger response.

Question 21

what can cause aggregation of BCR?

Answer 21

highly repetitive structures can cause aggregration of BCR on the cells surface

Question 22

what is the role of T cells in B cell activation?

Answer 22

Needs T cells to help (cytokines and CD40L) to activate B cells

Question 23

what is the BCR triggered?

Answer 23

Monovalent soluble antigen can cause the Src family kinase Lyn to ‘disturb’ and open the BCR allowing signal transduction

Question 24

how does compliement act in BCR activation?

Answer 24

antigen bound to complimemt enhances the activation ability

Question 25

how does antigen bind to a BCR?

Answer 25

Antigen bound complement fragments C3d or C3b can bond to CD21, the antigen binds to the antibody resulting in cross-linking

Question 26

what is the intracellular signaling pathway in T cell activation?

Answer 26

-Tyrosine phosphorylation is an important mechanism by which transmembrane receptors transduce signals - Phosphotyrosine residues are recognised by proteins containing the phospho-dependent binding domain, SH2 - SH2 domain proteins can act to recruit other molecules, as enzymes or as trancription factors

Question 27

what are ITIMs and ITAMs?

Answer 27

Phosphorylation sites in immune receptors

Question 28

what are ITIMs?

Answer 28

Immunoreceptor tyrosine-based inhibitory motifs

Question 29

what are ITAMs?

Answer 29

Immunoreceptor tyrosine-based activation motif

Question 30

what are Src family kinases?

Answer 30

Protein tyrosine kinases Fyn, Blk and Lyn associate with resting receptors After ligand binding and receptor clustering the kinases phosphorylate tyrosines in ITAMs on Igalpha and Igbeta

Question 31

what are the features of Syk kinase?

Answer 31

Syk has 2 SH2 domains and binds to pITAMs on Igbeta Syk becomes activated by binding ti the phosphorylated site

Question 32

what does syk activation induce?

Answer 32

formation of a membrane-associeated signalling complex

Question 33

what is BLNK?

Answer 33

a scaffold protein

Question 34

what is the structure of BLNK?

Answer 34

has multiple sites for tyrosine phosphorylation

Question 35

what phosphorylates BLNK?

Answer 35

Syk

Question 36

what is the role of BLNK once it is phosphorylated?

Answer 36

pBLNK recruits other Sh-2 domain proteins to form the multiprotein signalling complex

Question 37

what is Bruton's tyrosine kinase?

Answer 37

a protein that comes into the complex once BLNK is phosphorylated by Syk

Question 38

what activates the PLCg2 pathway?

Answer 38

Bruton's tyrosine kinase

Question 39

what is the end result of the PLCg2 pathway?

Answer 39

upregulation of transcription factors

Question 40

what does activation of transcription factors lead to?

Answer 40

- increased B cell maturation - increased activation

Question 41

what does activation of the PI3K pathway require?

Answer 41

Phosphorylation of CD19 (B cell co-receptor) by LYN

Question 42

what does PI3K pathway activation lead to?

Answer 42

Leads to PIP3 production This recruits BCR signalling components to the plasma membrane and activates them

Question 43

what is the main mediator of the PI3K pathway?

Answer 43

Serine/ threonine kinase AKT is the main mediator of the PI3K pathway

Question 44

what does the PI3K pathway regulate?

Answer 44

Cell cylce Apoptosis

Question 45

what is the role of AKT in the PI3K pathway?

Answer 45

AKT induces pro-survival genes through IKK and mTOR

Question 46

what is mTOR?

Answer 46

kinase that controls cell growth and proliferation

Question 47

what is the role of the PI3K pathway?

Answer 47

-promotes growth -promotes survival

Question 48

what activates the ERK pathway?

Answer 48

RAS activation

Question 49

what is ERK?

Answer 49

a MAPkinase

Question 50

how is ERK activated?

Answer 50

it is phosphorylated due to activated of RAS and this causes it to form a dimer Dimerization allows translocation to the nucleus

Question 51

what is the role of ERK in the nucleus?

Answer 51

-proliferation -Survival -Differentiation

Question 52

how is ERK activated?

Answer 52

it is phosphorylated due to activated of RAS and this causes it to form a dimer Dimerization allows translocation to the nucleus