B Cells: Development Flashcards

1
Q

phase 1

A

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

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2
Q

phase 2

A

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

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3
Q

phase 3

A

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

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4
Q

phase 4

A

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

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5
Q

phase 5

A

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

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6
Q

phase 6

A

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

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7
Q

are B cells stockpiled?

A

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

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8
Q

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

A

Early pro-B cell

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9
Q

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

A

Late pro-B cell

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10
Q

what is the first checkpoint of B cell development?

A

after the heavy chain has rearranged

Late pro-B cell

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11
Q

when is the heavy chain made?

A

Large pre-B cell

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12
Q

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

A

small pre-B cell

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13
Q

when is the second checkpoint of B cell maturation?

A

after the light chain has rearranged

small pre-B cell

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14
Q

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

A

IgM

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15
Q

what is the order of B cell development?

A

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

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16
Q

Stromal cells interact and drive B cell development how?

A
  • 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
17
Q

Does the D-J rearrange happen on both chromosomes?

A

yes

*early pro-B cell

18
Q

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

A

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

19
Q

Early Pro-B cell

A

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

20
Q

Late-Pro-B cell

A

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

21
Q

what is the pre B cell receptor?

causes transition form Pro to Pre B cell

A

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

22
Q

Ig alpha and beta

A

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

23
Q

why is allelic exclusion important?

A

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

24
Q

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

A

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

25
small Pre-B cells light chains are rearranged sequentially how?
4-5 recombinations per chromosome kappa then lambda -approxiamately 85% of small pre-B cells survive -Functional antibody expressed on the cell surface (IgM)
26
what are the two checkpoints in B cell developement?
- 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
27
what is negative selection
exposure to self antigen and ensures tolerance - central tolerance(bone marrow) - peripheral tolerance(soluble self antigen)
28
if a B cell binds to self what happens?
has a chance to rearrange again, if this fails again then it under goes apoptosis
29
what are the 3 fates negative selection
- light chain reorganization - apoptosis - anergy(nonfunctional cells)
30
Immature B cells migrate to lymphoid tissues through what?
a High endothelial venule (HEV)
31
Where do B cells mature?
in secondary lymphoid tissues and reside in the the primary lymphoid follicles
32
what draws immature B cells to secondary lymphoid tissues?
CCL 21 and CCL19 released by stromal dendritic cells
33
what does CXCL 13 do?
attracts B cells into the primary follicle
34
what drives the maturation of B cells in the primary follicle?
interactions with follicular dendritic cells and cytokines via BAFF **positive selection
35
A mature naive B cell has what expression of IgD and IgM?
increased IgD decreased IgM *now can circulate in lymph, blood, and secondary tissues
36
Positive selection of B cell
lymph node localization | BAFF signaling
37
what are the steps of B cell activation | 4 steps
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