Glossary of Immunology lecture 10 Development of B Cells

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What are the four phases of B cell development
1. Development from stem cells in the bone marrow
2. Elimination of self-reactive cells
3. Migration to the periphery
4. Terminal antigen-stimulated differentiation into effector and memory cells
Where do the first two phases of B cell development take place
The bone marrow
What is the most important aspect of the first stage of B cell development
The stepwise process by which functional BCR/Ig genes are formed. This ensures that the B cell produces Ig of a single specificity.
B cell interactions with the bone marrow stroma are required for what
To maintain viability and proliferation of the developing cells
What are the three families of an Ig gene segment
Variable (V), Joining (J), Diversity (D)(Heavy chain only)
What is somatic recombination
The process by which V, D, and J segments are brought together to form functional BCR/Ig.
What makes up the recombination machinery
Recombination signal sequences (RSS) in the DNA; Recombination activating genes (RAG-1, RAG-2); DNA repair enzymes
How is additional junctional diversity generated in the variable regions
By the imprecise nature of DNA cleavage and repair at the junctions between recombined gene segments
What is allelic exclusion
Expression of a functional heavy chain at the cell surface inhibits further heavy chain recombination
What is a surrogate light chain
Because the heavy chain cannot be expressed on the cell surface without a light chain, a surrogate light chain is produced to allow heavy chain expression before recombination has occurred at the light chain loci.
What is a pre-B cell receptor
The complex formed by the newly recombined heavy chain and the surrogate light chain
What are the developmental stages of a B cell
1. Stem cell
2. Early pro-B cell
3. Late pro-B cell
4. Large pre-B cell (characterized by the pre-B cell receptor)
5. Small pre-B cell
6. Immature B cell
7. Mature B cell
Developing B cells require interactions with what for their continued survival and proliferation
Bone marrow stroma. Important stromal components include adhesion molecules and growth factors such as stem cell factor (SCF) and Interleukin-7
What two processes contribute to the removal or inactivation of auto-reactive B cells
Clonal deletion (B cells that respond to self antigens while still in the bone marrow)
B cell anergy (B cells that resond to soluble self antigens are signaled to enter a harmless, non-responsive state)
Where do naive immature B cells migrate to after leaving the bone marrow
Secondary lymphoid tissues
How do B cells gain access to secondary lymphoid tissues
Via high endothelial venules
Where do B cells concentrate in the lymph nodes
In the lymph node cortex, called primary lymphoid follicles
What cells do B cells interact with in the B cell area
Follicular dendritic cells, which provide survival signals to the B cells
At what point is B cell development arrested
An immature, naive state until the B cell encounters the specific antigen to which the cell surface BCR/Ig can bind. Antigen recognition stimulates proliferation and terminal differentiation
What are germinal centers
Foci of proliferating B cells in the lymph node cortex
What is a secondary lymphoid follicle
A lymphoid follicle containing a germinal center
What are plasma cells
Mature, terminally differentiated B cells that are committed to producing large quantities of Ig
Where do plasma cells primarily reside
In the medullary cords of the lymph modes and in the bone marrow
What does alternative splicing of heavy chain mRNA result in
Production of heavy chain proteins that lack the transmembrane region
What is affinity maturation
Switching to production of soluble Ig accompanied by refinement of the Ig specificity to produce Ig molecules of higher affinity
What is somatic hypermutation
A process where affinity maturation is achieved by rapid and random introduction of point mutations to the Ig variable regions
What enzyme is required for somatic hypermutation and affinity maturation
Activation-induced cytidine deaminase (AID)
What is isotype switching (class switching)
A process where Ig molecules with different functions are produced by pairing the variable antigen-binding region of the Ig molecule with different heavy chain constant regions that possess different properties
What are the different heavy chain constant regions encoded by
A cluster of C gene segments
What are some diseases associated with B cell abnormalities
1. B cell neoplasias (Acute lymphoblastic leukemia, Pre-B cell leukemia, Burkitt's lymphoma, Hodgkin's lymphoma, Multiple myeloma[Bence-Jones proteins])
2. B-cell mediated autoimmunity
3. B cell immunodeficiencies

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