Quiz 5 - German - B Cell Development Flashcards by Brennan Stringam

Tell me the B cell development timeline including the heavy and light chain designations.

Bone Marrow

Stem cell - germline, germline
Early pro-B - germline, germline
Late pro-B - DJ, germline
Large pre-B - VDJ, germline
Small pre-B - VDJ, germline
Immature B cell - VDJ, VJ

Lymphoid organs/circulation

Immature B cell (IgM, no IgD)
Immature B cell (High IgM, low IgD)
Mature, naive B cell (Low IgM, High IgD)
Antigen activated B lymphoblast
Antibody-secreting plasma cell
Memory cell

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Are B cells stockpiled?

NAH TRICK

30 billion/day

Mature half-life: 50-100 days

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T/F - There is no immunoglobulin expressed during both the pro-B cell phases.

TRUE

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Where is the checkpoint for the functional heavy chain?

B/t late pro-B cell and large pre-B cell

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Where is the checkpoint for the function light chain?

B/t small pre-B cell and immature B cell

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What drives B cell development?

Stromal cell interactions

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Stromal cells express ___________ molecules and ___________ factors.

Adhesion

Growth

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What is the event that moves the development of a B cell from early pro to late pro?

Once D and J have rearranged on chromosomes

*Once in late, V-DJ are rearranged on the first chromosome

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Tell me three things about the early pro B cell.

RAG proteins activated

Heavy chain D and J segments joined

Occurs on both chromosomes

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Tell me three things about the late pro B cell.

Heavy chain V and DJ segments joined

Occurs sequentially on chromosomes

2 chances for rearrangement

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___-_____ signaling causes the transition from pro to pre B cell.

Pre-BCR

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What is allelic exclusion?

Functional heavy chain produced by only one chromosome

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Tell me about late pro-B cell in terms of pre-BCR.

VDJ rearrangement produces pre-BCR

Pre-BCR expressed in the ER

Surrogate light chain expressed

IgAlpha/Beta expressed

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Tell me about IgBeta signaling.

Checkpoint clearance

Turns OFF RAG proteins

Initiates cell division

Allelic exclusion

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What is affinity?

What is avidity?

Affinity - Likelihood of binding

Avidity - Strength of binding

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No allelic exclusion would give heterogeneous B-cell receptors with _____ avidity binding.

Low

What moves B-cell development from large pre-B cell to small pre-B cell?

CELL DIVISION

100 small pre-B cells

RAG genes reactivated

Unique recombination per cell

T/F - Light chains are rearranged sequentially.

TRUE

How many recombination attempts are possible per chromosome?

4 to 5

What comes first, kappa or lambda?

Kappa, then lambda

Approximately ___% of small pre-B cells survive.

85%

When are RAG proteins turned off?

Immature B cell has functional antibody expressed on the cell surface

When does H-chain gene rearrangement occur?

When does L-chain gene rearrangement occur?

When does rearrangement cease?

H-chain - Early and late pro-B cell

L-chain - Pre-B

Immature B cell - B/c the antibody is expressed on the cell surface

What is happening with chromosomes during the early pro-B cell phase?

D-J rearrangements on both chromosomes

What happens to the chromosomes during the late pro-B cell phase?

V-DJ rearrangement on 1st chromosome -If productive, moves to Pre-B cell -If nonproductive, V-DJ rearrangement on 2nd chromosome —If productive, moves to Pre-B cell —If nonproductive, moves to apoptosis

What happens to the chromosome during the Pre-B cell phase?

Kappa gene rearranged on 1st chromosome -If productive - Cell moves to immature B cell and expresses mew and kappa -If nonproductive - It rearranges kappa on 2nd chromosome —If productive - cell moves to immature B cell and expresses mew and kappa —If nonproductive - Cell rearranges lambda gene on first chromosome -If productive - Cell moves to immature B cell and expresses mew and lambda -If nonproductive - Cell rearranges lambda on 2nd chromosome —If productive - Cell moves to immature B cell and expresses mew and lambda —If nonproductive - Apoptosis

What do check points do?

Ensure immunoglobulin integrity

What are the two types of tolerance?

Central -Inability to respond to self antigen in bone marrow Peripheral -Inability to respond to self antigen in the periphery *If a cell in the marrow reacts with self antigen, then the immature B cell is retained in the marrow **If a cell does not react with self antigen in the marrow, then it moves to the blood and expresses IgD and IgM

Negative selection has three flavors. Name and describe them.

Light chain reorganization -Self-antigen cuts off IgM and cell makes new light chain and an IgM with different specificity Apoptosis -New light chain is tested again, if no self reaction, it goes to blood. If reaction, it continues changing light chain and is retested. If it fails the test again, APOPTOSIS Anergy -Basically, the body allows a lame B-cell into the periphery where it doesn’t bind anything and then it dies quickly

Where do immature B cells migrate to?

Lymphoid tissues, like lymph nodes Also, speed and GALTs

Tell me the process of B-cell maturation w/in secondary lymphoid tissues.

CCL21 attracts immature B cells to high endothelial venule CCL21 and CCL19 attract B cells into lymph node CXCL12 attracts B cells into the primary follicle Interaction with follicular dendritic cells and cytokines drive the maturation of immature B cells —Positive selection - Lymph node localization and B cell activating factor Mature B cells recirculate b/t lymph, blood, and secondary lymphoid tissues —Increased IgD expression and decreased IgM expression

T/F - B cells are activated in lymphoid tissues.

TRUE

What are the 4 steps of B cell activation in lymphoid tissues?

1 - Antigen exposure in the cortex 2 - Interaction with T cells 3 - Migration, secondary lymphoid follicle formation, and colonial expansion 4 - Plasma cell production and antibody secretion