B Cells: Development

Question 1

phase 1

Answer 1

generation of diverse and clonally expressed B-cell receptors in the bone marrow

Question 2

phase 2

Answer 2

alteration, elimination or inactivation of B-cell receptors that bind to components of human body.
*negative selection

Question 3

phase 3

Answer 3

promotion of a fraction of immature B cells to become mature B cells in the secondary lymphoid tissues
* positive selection

Question 4

phase 4

Answer 4

recirculation of mature B cells between lymph, blood, and secondary lymphoid tissues

Question 5

phase 5

Answer 5

activation and clonal expansion of B cells by pathogen-derived antigens in the secondary lymphoid tissues

Question 6

phase 6

Answer 6

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

Question 7

are B cells stockpiled?

Answer 7

NO, they are constantly replaced
30 billion/day
half life is 50-100 days thus population is winnowed down

Question 8

when does the D-J of the heavy chain rearrange?

Answer 8

Early pro-B cell

Question 9

when dos the DJ-V of the heavy chain rearrange?

Answer 9

Late pro-B cell

Question 10

what is the first checkpoint of B cell development?

Answer 10

after the heavy chain has rearranged

Late pro-B cell

Question 11

when is the heavy chain made?

Answer 11

Large pre-B cell

Question 12

when does the V-J rearrange of the light chain?

Answer 12

small pre-B cell

Question 13

when is the second checkpoint of B cell maturation?

Answer 13

after the light chain has rearranged

small pre-B cell

Question 14

What is expressed on the surface of an immature B cell?

Answer 14

IgM

Question 15

what is the order of B cell development?

Answer 15

early pro, late pro, large pre, small pre, immature

Question 16

Stromal cells interact and drive B cell development how?

Answer 16

• express adhesion molecules and growth factors
• B cell receptor expression changes with progression through development
• Pro-B cells are programmed to die in the absence of survival signals

Question 17

Does the D-J rearrange happen on both chromosomes?

Answer 17

yes

*early pro-B cell

Question 18

If the V-DJ doesn’t happen on one chromosome what happens?

Answer 18

it gets another chance on the other chromosome, if this also fails then the cell dies. Junctional diversity errors result in non successful formation of heavy chain
*Late pro-B cell

Question 19

Early Pro-B cell

Answer 19

RAG proteins activated
heavy chain D and J segments joined
occurs on both chromosomes

Question 20

Late-Pro-B cell

Answer 20

heavy V and DJ segments joined
occurs sequentially on chromosomes
two chances for RAR
*first checkpoint happens now for functional heavy chain

Question 21

what is the pre B cell receptor?

causes transition form Pro to Pre B cell

Answer 21

it is expressed in the ER
**surrogate light chain expressed and ensures a light chain can bind
Ig alpha and beta expressed(allows signaling)

Question 22

Ig alpha and beta

Answer 22

checkpoint clearance
turns of RAG proteins
initiates cell division
-Allelic exclusion(heavy chain only from one chromosome)

Question 23

why is allelic exclusion important?

Answer 23

ensures specificity of the heavy chain not allowing for a mixture of heavy chain production

Question 24

Once the late pro-B cell has made it through the checkpoint and transitions into a Large -Pre-B cell what happens?

Answer 24

cell division:
100 small pre-B cells
RAG genes activated
unique recombination per cell(light chain)

Question 25

small Pre-B cells light chains are rearranged sequentially how?

Answer 25

4-5 recombinations per chromosome
kappa then lambda
-approxiamately 85% of small pre-B cells survive
-Functional antibody expressed on the cell surface (IgM)

Question 26

what are the two checkpoints in B cell developement?

Answer 26

• functional heavy chain(pre B cell receptor) and happens between early and late Pro B-cells
• functional light chain
• *both signal through Ig alpha and beta

Question 27

what is negative selection

Answer 27

exposure to self antigen and ensures tolerance

• central tolerance(bone marrow)
• peripheral tolerance(soluble self antigen)

Question 28

if a B cell binds to self what happens?

Answer 28

has a chance to rearrange again, if this fails again then it under goes apoptosis

Question 29

what are the 3 fates negative selection

Answer 29

• light chain reorganization
• apoptosis
• anergy(nonfunctional cells)

Question 30

Immature B cells migrate to lymphoid tissues through what?

Answer 30

a High endothelial venule (HEV)

Question 31

Where do B cells mature?

Answer 31

in secondary lymphoid tissues and reside in the the primary lymphoid follicles

Question 32

what draws immature B cells to secondary lymphoid tissues?

Answer 32

CCL 21 and CCL19 released by stromal dendritic cells

Question 33

what does CXCL 13 do?

Answer 33

attracts B cells into the primary follicle

Question 34

what drives the maturation of B cells in the primary follicle?

Answer 34

interactions with follicular dendritic cells and cytokines via BAFF
**positive selection

Question 35

A mature naive B cell has what expression of IgD and IgM?

Answer 35

increased IgD
decreased IgM
*now can circulate in lymph, blood, and secondary tissues

Question 36

Positive selection of B cell

Answer 36

lymph node localization

BAFF signaling

Question 37

what are the steps of B cell activation

4 steps

Answer 37

1. antigen exposure in cortex
2. interaction with T cell (isotype of Ab)
3. migration to germinal center
4. plasma cell production and memory cells