B Cell Development

Question 1

What is the general steps of B cell development (7)

Answer 1

1.Hematopoietic stem cell
2.Common lymphoid progenitor
3.Progenitor B-cell
4. Pre B-cell
5. Immature B-cell
6.Mature (naïve) B-cell
7. Activated B-cell – peripheral lymphoid organ
Antibody secreting plasma cell
Memory B-cell

Question 2

In what stage does b cell receptor rearrangement occur

Answer 2

Pro B cell stage

Question 3

How are b cell receptors set up

Answer 3

made of 2 identical antigen binding sites

2 light(a) and 2 heavy(b) chains

Question 4

What are the 2 states the b cell receptor can be in

Answer 4

expressed on cell surface

or recreated (antibody)

Question 5

What chain is generated first in the pro b cell stage

Answer 5

Heavy chain

Question 6

How is the B chain (variable region) created

Answer 6

VDJ recombinase catalyzes D genes (12) combining with J (23) genes and then it recombines with the V section

Question 7

How is the heavy chain tested (and stage of development this is done)

Answer 7

Pre B stage the heavy chain is tested on cell surface using surrogate light chain and must be able to interact with IgB and igA

Question 8

At what stage does the light chain start developing

Answer 8

Pre b stage

Question 9

What are the two light chain genes to choose from and chromosome they on

Answer 9

Kappa light chain (chromosome 2)

Lamda light chain (chromosome 22)

will have 2 of one or the other

Question 10

How does recombination occur on the light chain

Answer 10

Only has V and J gene segments that recombine (with 12/23 rule)

Question 11

if the pre b cell has good heavy and light chains what will happen and what stage will it move to

Answer 11

Proliferate many times

-move from large to small pre b cell stage

Question 12

What configuration will b cells have on its surface when its immature

Answer 12

iGm receptor

Question 13

What happens in positive selection of b cells

Answer 13

b cells are positively selected when signalling occurs through the pre b receptor (heavy chain testing)

Question 14

what happens in negative selection of immature b cells

Answer 14

involves interactions between the default IgM receptor and self antigens

Question 15

what are the options for negative selection

Answer 15

1. no rxn to self- mature
2. rxn to multivalent self molecules resulting in clonal deletion/receptor editing
3. rxn to self molecules (non cross linking) becoming anergia

Question 16

in what area of the lymph node is the b cell activated

Answer 16

germinal center in primary lymphoid follicle

Question 17

Overall steps on how b cell are activated

Answer 17

B cell binds to antigen that it is specific to and is internalized by b cell and processed on MHC2 which attached to helper t cell (t cell provides 3 signals)

Question 18

What are the 3 signals provided to the b cell by the t cell to activate it

Answer 18

1. Th1/2 binds to MCH + antigen
2. CD40(on b) binds to CD40L
3. Th1 releases IFN + Th2 releases IL4

Question 19

Once b cells recieve all 3 signals they may differentiate into (2)

Answer 19

1. Plasma cells (antibody secreting cells)

2. Memory b cells

Question 20

what is somatic hypermutation and when does it happen

Answer 20

As b cell proliferates VDJ gene segments can undergo random mutation which could change binding strength to antigens

(ONLY HAPPENS IN B CELLS)

Question 21

What is isotype switching and when does it occur

Answer 21

When b cells are proliferating after activation

Heavy chain can express different constant genes which determine antibody effector function!

Question 22

What is responsible for isotype switching + enzyme

Answer 22

specific cytokines

enzyme: activation induced cytidine deaminase

Question 23

What are follicular helper t cells important for (4) + effector cytokine responsible

Answer 23

interact with activated b cells and:

1. form germinal centers
2. Somatic hypermutation
3. b cell survival
4. class switching

-Il21

Question 24

Generally how do memory b cells work

Answer 24

when a memory b cells bar binds to its epitope it may differentiate into antibody secreting plasma cells