3/2/17 GERMAN B Cell Development TEST #2 Flashcards
T/F B cells are stockpiled an not constantly replaced
False
-B cells are not stockpiled and constantly replaced
What is the Phase one in the B Cell life?
-Generation of diverse and clonally expressed B-cell receptors in bone marrow
What is Phase 2 in the B cell life?
-Alteration, elimination or inactivation of B-Cell receptors that bind to components of the human body (negative selection)
What is Phase 3 in the B cell life?
-(occurs in the bone marrow and periphery) Promotion of a fraction of immature B cells to become mature B cells in secondary lymphoid tissues (Positive selection)
What is Phase 4 in the B cell life?
-Recirculation of mature B cells between lymph, blood, and secondary lymphoid tissues (searching for infection)
What is Phase 5 in the B cell life?
-Activation and clonal expansion of B cells by pathogen derived antigens in secondary lymphoid tissues
What is Phase 6 in the B cell life?
-Differentiation to antibody-secreting plasma cells and memory B cells in secondary lymphoid tissue (Attacking infection)
What is the half life of a B-cell once it matures?
-50-100 days
What does Phase 3.5 to Phase 6 occur in the B cell life?
-Periphery
What class of antibody is an immature B cell?
- IgM (1st)
- IgD (2nd)
When you have an antigen activated B lymphoblast what occurs?
- Isotype switching that leads to antibody-secreting plasma cells
- Clonal expansion
What is the first stage in B cell development that you get rearrangement of the heavy chain?
-Early pro-B cell
What two things occur in the Pro-B cell stages that are involved in rearrangement
- Junctional Diversity
- Genetic Recombination
What is the checkpoint between the Pro B cell and the Pre B cell?
-A Functional heavy chain
What is the checkpoint between the pre B cells and immature B cell?
-Functional light chain
What chain is rearranged in the pre B-cell stage?
-Light chain
T/F Stromal cells express adhesion molecules and growth factors
True
T/F B cell receptor expression does not change with progression through developmental stages
False
-It changes with progression
If you don’t produce a functional heavy chain (pro-B cell) what happens to the B cell?
-It dies
What happens with the RAG proteins in the early pro-B cell?
-RAG proteins are activated
What happens with the regions on the heavy chain in the early PRO-B cell stage?
-Heavy chain D and J segments joined
T/F In the early pro-B cell the rearrangement occurs on both chromosomes
True
In the late Pro-B cell what heavy chain segments join?
-Heavy chain V and DJ segments join
T/F Pre-B Cell Receptor signaling causes the transition from Pro to Pre B cell
True
What does the VDJ produce?
-Pre-BCR
Where is the Pre-BCR expressed?
-ER
What does the Pre-BCR allow the heavy chain to do?
-interact to the Ig-Alpha and Ig-Beta
When the heavy chain interacts with what does it pass a checkpoint clearance?
-Ig-Beta
When you have Ig-Beta signaling you have three things that occur, What are they?
- Turns off RAG proteins
- Initiates cell division
- Allelic exclusion
What is allelic exclusion?
-It is when a functional heavy chain is produced by only one chromosome
What does the Late pro-B cell become?
-Large pre-B cell
What is responsible for initiating light chain rearrangement?
-Pre-B cells
When you go from the Large pre-B cell to the small pre-B cell what occurs?
- Cell division
- RAG genes reactivated
- Unique recombination
How many recombination attempts are possible per chromosome in the light chain?
-4-5
What are the two types of chromosome genes on the light chain?
- Lambda
- Kappa
After you have the heavy chain and light chain rearrangement what must you have to not experience apoptosis?
-A B-cell receptor via (Ig alpha and Ig Beta)
If an immature B-cell doesn’t react with a self antigen what happens?
-It is released into the blood
What are the two types of tolerance of B-cells
- Central tolerance (occurs in the Bone marrow)
- Peripheral tolerance (occurs outside the bone marrow)
What are the three fates of a B cell that bound self cells?
- Light Chain reorganization to try and become functional
- Apoptosis
- Anergy (Still alive but shut down all signaling and activating process)
Where do B-cells mature?
-Secondary lymphoid tissues (spleen, lymph nodes, GALTS)
How do immature B cells enter into they lymphoid tissues?
-High Endothelial venule
What two chemokines attract B cells into the lymph node?
- CCL 21
- CCL 19
Interactions with what cells drives the maturation of immature B cells?
-Follicular dendritic cells
What two things are involved in positive selection for a B cell?
- Lymph node localization
- BAFF signaling
Where are B cells activated?
-Lymphoid tissues
When the B cell interacts with T cells and becomes activated what occurs?
-Migration, secondary lymphoid follicle formation, and clonal expansion
What occurs in the Germinal centers?
-Plasma cell production and antibody secretion
What do Dysfunctional B cell developments cause?
-Cancers
