Quiz 5 - German - B Cell Development Flashcards
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
Are B cells stockpiled?
NAH TRICK
30 billion/day
Mature half-life: 50-100 days
T/F - There is no immunoglobulin expressed during both the pro-B cell phases.
TRUE
Where is the checkpoint for the functional heavy chain?
B/t late pro-B cell and large pre-B cell
Where is the checkpoint for the function light chain?
B/t small pre-B cell and immature B cell
What drives B cell development?
Stromal cell interactions
Stromal cells express ___________ molecules and ___________ factors.
Adhesion
Growth
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
Tell me three things about the early pro B cell.
RAG proteins activated
Heavy chain D and J segments joined
Occurs on both chromosomes
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
___-_____ signaling causes the transition from pro to pre B cell.
Pre-BCR
What is allelic exclusion?
Functional heavy chain produced by only one chromosome
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
Tell me about IgBeta signaling.
Checkpoint clearance
Turns OFF RAG proteins
Initiates cell division
Allelic exclusion
What is affinity?
What is avidity?
Affinity - Likelihood of binding
Avidity - Strength of binding
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
