B Cells: Development Flashcards
Where do the first 3 phases of B cell development happen?
Bone Marrow
Where do the last 3 phases of cell development and a little bit of the 3rd happen?
In the periphery
B cells are _______ and ______
- Diverse
2. Specific
T/F B cells are stockpiled in the lymphatic system
FALSE, they are NOT stockpiled but constantly replaced
How many B cells are made per day?
30 billion
What is the mature half life of a B cell?
50-100 days
Antibody repertoire of a B cell undergoes _______
Constant evolution
B cell populations are _____ at each phase
Winnowed (thinned out?)
In the bone marrow, what does the progression of a B cell look like?
- Stem cell
- Early pro-B cell
- Late pro-B cell
- Large pre-B cell
- Small pre-B cell
- Immature B cell
In the Secondary lymphoid organs and circulation what does the progression of a B cell look like?
- Immature B cell
- Mature Naive B cell
- Antigen-Activated B lymphoblast
- Antibody-Secreting plasma cell
- Memory cell
T/F Early and Late pro B-Cells are rich in immunoglobulin
FALSE, they have no immunoglobulin
What type of cell interactions drive B cell development?
Stromal cell
Stromal cells express ________ and __________
- Adhesion molecules
2. Growth factors
T/F Pro-B cells are programmed to die in the absence of survival signals
True
______ receptor expression changes with progression through developmental stages
B cell
At what stage in development does a B cell leave the bone marrow?
Immature B cell
What is happening in an Early pro-B cell regarding Heavy chain rearrangement?
- RAG proteins Activated
- Heavy chain D and J segments joined
- Occurs on both chromosomes
What is happening in a Late pro-B cell with regards to heavy chain rearrangement?
- Heavy chain V and DJ segments joined
- Occurs sequentially on chromosomes
- Two chances for rearrangement
What causes the transition from Pro to Pre B cell?
Pre-BCR signaling
T/F A functional heavy chain is produced by only one chromosome
True
*This is called Allelic exclusion
What does IgBeta signaling do in the checkpoint from pro to pre B cell?
- Checkpoint clearance
- Turns off RAG proteins
- Inintiates Cell division
- Allelic Exclusion
In the transition from Pro to pre B cell, what is happening with the Late Pro-B cell?
- VDJ rearrangement prodeucese pre-BCR
- Pre-BCR expressed in the ER
- Surrogate light chain expressed
- Igalpha/beta expressed
What would happen if you did not have allelic exclusion
Heterogenous B cell receptors with low-avidity binding
Each large pre-B cell becomes about how many small pre-B cells?
100
Going from Large to small pre-B cell what happens to the RAG genes?
They are reactivated
T/F Each small pre-B cell has a unique recombination per cell
True
In Light chain rearrangement, how many recombination attempts are there per chromosome?
4 to 5
Approximately how many small pre-B cells survive?
85%
Where are the two different checkpoints in B Cell development in the bone marrow?
- Pre-B cell receptor
- Selects for functional heavy chains
- B-Cell receptor
- Selects for functional light chains
Immature B cells undergo __________
Negative selection
Exposure to self antigen ensures _______
Tolerance
What is Tolerace?
Inability to respond to self antigen
What are the two types of Tolerance?
- Central
2. Peripheral
What is Central tolerance?
Tolerance acquired in bone marrow
What is Peripheral tolerance?
Tolerance acquired in the periphery
What are the 3 fates of a B cell in negative selection?
- Light chain reorganization
- Apoptosis
- Anergy
What is Anergy?
Cells that are still alive but essentially shut down all their signaling and activating processes
*Usually die after about 3-5 days
Immature B cells migrate to ______
Lymphoid tissues
Where to B cells mature?
In secondary lymphoid tissues
Give 3 examples of secondary lymphoid tissues where B cells can mature
- Spleen
- Lymph nodes
- GALTs
What does HEV stand for?
High Endothelial Venule
How do B cells enter into lymph nodes?
HEV
T/F B cells are draw to secondary lymphoid tissues by chemokines
True
What are the steps of B cell activation in the Lymphoid tissues?
- Antigen Exposure in the cortex
- Interaction with T cells
- Migration, secondary lymphoid follicle formation, and clonal expansion
- Plasma cell production
What does the IgD/IgM expression look like in a Mature Naive B cell?
- Increased IgD expression
- Decreased IgM expression
What are the steps of B cell maturation within secondary lymphoid tissues?
- Chemokine CCL21 attracts immature B cells to HEV
- Chemokins CCL21 and CCL19 attract B cells into Lymph Node
- Chemokine CXCL13 attracts B cells into the primary follicle
- Interactions with follicular dendritic cells and cytokines drives the maturation of immature B cells
- Mature B cells recirculated between lymph, blood, and secondary lymphoid tissues
Name two attributes of Positive Selection
- Lymph Node Localization
2. BAFF signaling