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53 Cards in this Set

  • Front
  • Back
Where does B cell development mainly occur?
Mainly in the bone marrow
Progenitors committed to the B-cell lineage give rise to pro-B cells as a result of what?
The direct interaction of stromal cells.

VCAM-1 adhesion molecule on the stromal cell and the VLA-4 adhesion molecule on the pro-B cell. Other cell adhesion molecules (CAMs) are also involved.
Once contact has been made between VCAM-1 and VLA-4, what is the receptor on pro-B cells that interacts with stem cell factor (SCF)?

Where is SCF located?
C-kit

located on the stromal cell surface
What interleukin drives the maturation process of B cells?
IL-7
IL-7 receptors are on what stage of B cells?
pre-B cell
T/F

Adhesion molecules on the pre-B cells are upregulated allowing the pre-B cells to detach from the stromal cells.
False!

Adhesion molecules on the pre-B cells are DOWNregulated allowing the pre-B cells to detach from the stromal cells.
T/F

IL-7 is REQUIRED for continued growth and maturation to the immature and mature B-cell stages.
True!
What cells, that provide microenvironments for B cell maturation, are nonlymphoid cells located in the bone marrow?
Stromal cells
What are the 2 primary functions of stromal cells?
1. Interact directly with pro-B cells and pre-B cells

2. Secretion of several cytokines, including IL-7 (IL-7 supports the developmental process of B-cells.
Immunoglobulin genes are (single/multiple)-gene segments in the germ-line DNA.
Multiple
Are immunoglobulin genes carried in germ or somatic cells?
Germ cells
When does the rearrangement of immunoglobulin genes into functional genes occur?
During the B-cell maturation process
What is the earliest identifiable cell in the B-cell maturation process?
Pro-B cell
The heavy chain V(H) to D(H)J(H) gene rearrangement occurs in the (early/late) pro B-cell.
Late
The heavy chain D(H) to J(H) gene rearrangement occurs in the (early/late) pro B-cell.
Early
After heavy-chain rearrangement of the pro-B cell is completed, what type of cell is it?

What does the B cell begin to express at this stage?
Pre-B cell

a μ chain
The large pre B-cell expresses what receptor?
Pre B-cell receptor
The membrane μ chain in pre B-cells is associated with a surrogate (light/heavy) chain and what polypeptides?
Light; Ig(alpha) and Ig(beta) polypeptides
T/F

Surrogate light chains are true Ig proteins.
False!

They are NOT true Ig proteins
T/F

The membrane μ chain is expressed only in primitive B cell precursors.
True!
When does the cell halt heavy chain gene rearrangement and begin light chain gene rearrangement?
In small pre B-cells, when the μ chain and surrogate light chains reach the cell surface, it is believed that a signal is transducted back to the cell, indicating that a functional heavy chain protein is present.
In the small pre B-cell, when the μ chain and surrogate light chains reach the cell surface, why does the pre B-cell receptor disappear from the surface and the μ chain become trapped in the ER?
Because the production of surrogate light chains stops
The transition between which two stages requires light chain gene rearrangement?
Pre B-cell to immature B-cell
T/F

Multiple light chain isotypes are expressed on the membrane of a B cell.
False!

Only ONE light chain isotype is expressed on the membrane of a B-cell.
What are the 2 possible light chain isotypes?
Kappa and lambda
a) What commits the immature B cell to a particular antigenic specificity?

b) This is determined by what sequences?
a) Completion of the light chain gene rearrangement

b) Heavy chain VDJ sequence and light chain VJ sequence
What Ig is expressed on the cell surface of immature B-cells?
IgM
The development of immature B-cells to mature B-cells involves the production of 2 mRNA's. What does each one code for?
One for the μ chain and one for the delta chain
Development of immature B-cells to mature B-cells involves coexpression of which 2 Igs?
IgM and IgD
Early mature B-cells express low levels of IgD. When does expression of IgD increase?
After the cells are exported from the bone marrow to the lymphoid organs
What percent of B-cells produced in the bone marrow are actually recruited into the B-cell pool?

Why?
Only 10%

Due to negative selection
Describe negative selection in B-cell development.
When immature B-cells react to self antigens, crosslinking of the membrane autoantibodies occurs, leading to apoptosis.
T/F

If a B-cell receptor is self-reactive, the cell immediately undergoes apoptosis.
False!

First, the cell becomes arrested in development and continues light chain gene rearrangement (with low cell surface IgM), resulting in new receptor specificity. If it is still self-reactive, then it will undergo apoptosis. If not, the immature B cell will migrate to the periphery and mature.
What subset of B-cells does not conform to the normal pathway of development?
B1 cells
B1 cells are characterized by the expression of what on their cell surface?
CD5, a cell-surface glycoprotein usually considered a T-cell marker
B1 cells precede the development of what type of cells?
B2 cells, which are the majority subset of B cells
Do B1 cells have IgD on their cell surface?
They have very little or none
B1 cells arise from a stem cell that is active when?
During prenatal development
a) Rearranged heavy chain genes are more diverse in (B1/B2) cells.

b) Therefore, antibodies produced by (B1/B2) have low affinity and bind to many different antigens (polyspecificity).
a) B2

b) B1
B1 cells contribute to the production of antibodies that are against what?
common bacterial polysaccharides, NOT protein antigens
How are B1 cells maintained in the adult, since B1 cells are no longer developed in the bone marrow?
Maintained through self-replication in the peripheral circulation
Self-renewal of B1 cells is dependent upon which cytokine?
IL-10
Why are B1 cells commonly the source of B-cell tumors, such as chronic lymphocytic leukemia (CLL)?
Because of their ability for self-renewal
What happens to the mature, naive B-cell after B-cell development is complete?
It leaves the bone marrow and recirculates between the blood and secondary lymphoid tissues (lymph nodes, spleen, mucosa-associated lymphoid tissue, and lymph)
Where do mature, naive B-cells encounter antigens?
In the secondary lymphoid tissues (lymph nodes, spleen, mucosa-associated lymphoid tissue, and lymph)
Where are antigen-specific B-cells held?
In T-cell areas
What activates antigen-specific B-cells?
Antigen-specific CD4 T-helper cells
a) In the lymph nodes and spleen, what do activated B-cells do?

b) The change in the processing of heavy chain mRNA leads to the synthesis of what form of Ig instead of the membrane-bound form?
a) Proliferate and differentiate into antibody-secreting plasma cells.

b) Secreted form
What cells are specialized in the constitutive synthesis and secretion of antibody?
Plasma cells
T/F

Plasma cells' cellular organelles for protein synthesis are highly developed.
True!
What percent of the total protein from plasma cells is antibody?
10-20%
Plasma cells are terminally differentiated and cease to divide. They do not express cell-surface Ig or MHCII molecules.
Therefore, they (can/cannot) respond to antigen or interact with T-cells.
Cannot
How long is the life span for plasma cells?
About 4 weeks