Development of B-cells Flashcards
What are the six phases of B-cell development?
- Repertoire assembly
- Negative selection
- Positive selection
- Searching for infection
- Finding infection
- Attacking infection
The first 3 phases of B-cell development occur in ______, while the last 3 phases occur in ______.
- Bone marrow
- Blood vessels & lymphatics
Which hematopoietic cell can differentiate into a B-cell or T-cell?
Common lymphoid progenitor
Which of the following transmembrane proteins is the only one present on pluripotent hematopoietic stem cells?
- CD10
- CD34
- CD127
- CD19
CD34
True or false. When a B-cell precursor differentiates into a pro-B cell, it is no longer capable of self-renewal.
False. Pro-B cells are able to self-renew
Dh and Jh joining occurs in _____ cells
Early pro-B cells
Vh segment joins DJh segment in _____ cells
Late pro-B cells
Expression of functional μ chains occurs in _____ cells
Large pre-B cells
Light chain rearrangement and assembly with μ-chain occurs in ______ cells
Small pre-B cells
Membrane-bound IgM associates with Igα and Igβ in ______ cells
Immature B cells
Is the light chain or heavy chain more specific?
- Light chain is more specific
- If the body makes a good heavy chain, it will amplify the population of cells that can express that heavy chain so light chains can be processed from there
A ______ of growth factors and transcription factors drive immune cell differentiation
Gradient
___% of pre-B cells go on to become immature B-cells
50%
What is the function of stromal cells in bone marrow?
Make contact with maturing B cells and secrete growth factors for maturation
True or false. The default pathway for B-cell development is to die by apoptosis unless a survival signal is received.
True
What is the difference between productive and nonproductive rearrangement?
- Productive - complete and functional Ig produced from rearranged genes
- Nonproductive - rearrangement does not translate into a functional Ig
What is the consequence of not having a functional Rag gene on either chromosome?
No rearragement can occur to create antibodies
What are the two criteria requirements for a pro-B cell to survive?
- Make a μ chain
- μ chain must be able to bind to a light chain (surrogate chain)
What are the two components of the surrogate light chain and function to mediate binding to receptors on stromal cells?
- VpreB
- λ5
How does a pro-B-cell initiate pre-B-cell receptor assembly?
- Igβ shuts down RAG gene transcription
- RAG proteins are degraded
- Chromatin Structural changes prevent gene rearrangement
What is allelic exclusion?
When a cell only expression one of its two copies of a gene
What is allelic exclusion?
Cell only expresses one copy of its two genes
What is the consequence of not having allelic exclusion in B-cell receptor formation?
Low avidity binding
___% of pre-B-cells have productive rearrangement
85%
RAG is expressed in what stages of B cell development?
- Early pro-B
- Late pro-B
- Large pre-B
- Immature B
Kit (growth factor receptor) is expressed in what stages of B-cell development?
- Stem cell
- Early pro-B
IL-7 (growth factor receptor) is expressed in what stages of B-cell development?
- Stem cell
- Early pro-B
- Late pro-B
- Large pre-B
CD25 (growth factor receptor) is expressed at what stages of B-cell development?
- Late pro-B
- Large pre-B
RAG1 and RAG2 are expressed in what stages of B-cell development?
- Early pro-B
- Late pro-B
- Immature B
λ5 and VpreB are expressed in what stages of B-cell development?
- Early pro-B
- Late pro-B
- Large pre-B
- Small pre-B
Of the two B-cell populations (B1 and B2), what is the difference between their modes of renewal?
- B1: self-renewing
- B2: replaced from bone marrow
B1 cells make up approximately ___% of B-cells
- ~5%
- Less diverse than B2
Why do B1 cells have a lower affinity for their antigens than B2 cells?
- Polyspecific
- Recognize bacterial polysaccharides, not proteins
Where are B-cells typically found?
- Blood
- Lymph
- Secondary lymphoid organs
- Bone marrow
____% of immature B-cells bind self-antigen
75%
In what stage of B cell development does negative selection occur?
Immature B-cells
What are the two potential fates of an immature B cell during negative selection?
- If it doesn’t recognize self-antigen, it ends the blood and expresses IgD and IgM
- If it does recognize self-antigen, it is retained in the bone marrow and given a second chance to rearrange light chain
_____ is a state of nonresponsiveness to an antigen
Anergy
What is the life span of an anergic B-cell vs. a normal B-cell?
- Anergic: ~1-5 days
- Normal: ~40 days
What are the possible fates for self-reactive B-cells in the bone marrow (central tolerance)?
- Receptor editing
- Apoptosis
- Anergy
What are the possible fates for self-reactive B-cells in the periphery? (Peripheral tolerance).
- Apoptosis
- Anergy
What is the function of high endothelial venules (HEV) in secondary lymph organs?
Delivery of B-cells (mature and immature) to lymph nodes in search of their corresponding antigens.
What is the function of chemokines?
Attracts B-cells
What chemokine is expressed in lymph node cortices and dendritic cells in lymph nodes?
CCL21
What chemokine is expressed solely on B-cells?
CCR7
What chemokine is expressed by dendritic cells in lymph nodes to attract B cells?
CCL19
______ are specialized stromal cells not of hematopoietic origin that secrete CXCL13 to attract B-cells to the primary follicle for maturation.
Follicular dendritic cells (FDCs)
