B-Cell activation, differentiation + memory

Question 1

Name the 5 stages in B-cell activation + differentiation.

Answer 1

1) Activation + antigen presentation
2) B-cell receptor clustering
3) Plasma cell differentiation
4) Somatic hypermutation (SHM)
5) Class switch recombination (CSR)

Question 2

Name the modes of activation.

Answer 2

a) T-cell dependent antigens presented to T(H) cells
b) T-cell independent antigens stimulate PRR on B-cell
c) other antigen fixes complement fragment C3d + binds complement receptors on B-cell

Question 3

Activated-B-cell response

Answer 3

~ activated B-cell goes to germinal centre where proliferation, SHM and CSR occurs
~ cells w/ correct affinity differentiate + exit germinal centre
~ cell become:
1) plasma cells
2) IgM+/IgD+ memory cells
3) class-switch memory B-cell

Question 4

Name the methods of antigen presentation to B-cells in lymph node.

Answer 4

1) antigen squeeze between sub capsular sinus (SCS) macrophages that line lymph node
2) leaky network of conduits, antigen sampled by follicular B-cells
3) taken up by SCS macrophage or follicular dendritic cell + passed on to B-cell

Question 5

B-cell receptor clustering

Answer 5

1) BCR recognises it’s specific antigen
2) receptors on B-cell surface membrane spread over antigen surface + then contract
3) causes internalisation of receptor-antigen complex + antigen presentation by B-cell to T-cell in lymph node

Question 6

Where do B-cells and T-cells interact in lymph node?

Answer 6

border between follicles (B-cell) and paracortex (T-cell)

Question 7

Somatic hypermutation (SHM)

Answer 7

~ occurs in germinal centres
~ B-cell differentiation continues w/ generation of somatically hyper mutated receptors that are subjected to antigen selection = high affinity to antibodies
~ SHM affects mutational hot sports in variable region genes in antibodies
~ mediated by enzyme AID

Question 8

AID

Answer 8

a.k.a. activation-induced cytidine deaminase (AID)
~ causes little breaks in the DNA through converting C to U
~ U gets removed causing abasic sites
~ this creates little changes when repaired

Question 9

Class switching recombination

Answer 9

~ initiated by AID altering cytosines to U in donor + acceptor switch (S) regions
~ causes abasic sites which are converted to ds break by mismatch repair proteins
~ DNA repair mechanisms ligase strands together but excise an intervening DNA sequence (changes the class)

Question 10

Name the 3 ways in which T-cells physically interact with B-cells.

Answer 10

1) binding to processed antigen with TCR
2) interactions between CD28 (T), CD80 (B) and CD86 (B)
3) interactions between CD40L (T) and CD40 (B)
~ this facilitates directional T-cell cytokine secretion which causes full B-cell activation

Question 11

Plasma cell differentiation

Answer 11

~ stimulation of primary B-cells at B/T border = some cells differentiate into plasma cells
~ plasma cells form primary foci + secrete IgM antibodies
~ other B-cells from antigen-stimulated clones migrate to primary follicles + form germinal centres

Question 12

Plasma cell

Answer 12

~ a fully differentiated B-lymphocyte which continually secretes antibodies (e.g. IgM)
~ ensure they constantly encounter antigens w/in blood
~ found in bone marrow

Question 13

Name the two types of memory B-cell.

Answer 13

~ memory B-cell

~ plasma cell

Question 14

Memory B-cell

Answer 14

~ produced during primary response from naïve B-cell that don’t differentiate into plasma cells
~ recirculating memory B-cells must be reactivated by antigen = higher, faster + stronger secondary response