Lymphocyte genetics and clonal expansion of B cells Flashcards
What is the role of B cells in the immune system?
produce antibodies that can bind to any potential antigen.
How does the immune system achieve diversity in antibody production?
V(D)J recombination where variable (V), diversity (D), and joining (J) gene segments are randomly mixed in developing B cells, leading to a vast array of unique antibodies.
Do B cells require antigens for their initial development?
No, B cell development is antigen-independent. B cells undergo V(D)J recombination and develop in the bone marrow before they have encountered an antigen
How is the specificity of B cells determined?
defined by genetic rearrangement during its development. Each B cell produces a unique antibody that defines its specificity
What is clonal selection in the context of B cells?
natural process by which a B cell with an antibody that successfully binds to an antigen is selected for. This B cell then proliferates, producing a clone of cells that all produce the same antibody specific to the antigen.
What is the “one cell-one antibody” rule?
Each B cell produces only one type of antibody. Each B cell clone will target a specific antigen.
What determines the specificity of B cell antigen receptors?
unique genetic mechanism during lymphocyte development in the bone marrow, creating millions of different receptor gene variants.
clonal selection theory
B cell progenitor gives rise to many pre-B cells, each with a unique specificity. Self-reactive pre-B cells are removed by clonal deletion, while specific immature B cells proliferate and differentiate when activated.
How does the immune system deal with self-reactive B cells?
Self-reactive B cells are altered or eliminated through a process called clonal deletion to prevent autoimmunity.
What are the two stages of B cell development?
maturation phase, where stem cells become mature naïve B cells, and a differentiation phase, where mature B cells become plasma cells or memory B cells upon antigen activation
What are the three main goals of B cell development?
- Generate a diverse array of antigen-binding receptors. 2. Alter or eliminate self-reactive B cells. 3. Promote the maturation of foreign-reactive B cells.
What happens to B cells after an antigen is eliminated?
specific B cells that were activated and proliferated form memory B cells, which remain in the body to provide a rapid response to future encounters with the same antigen.
How do B cells achieve diversity in their antigen receptors?
genetic rearrangement during their development in the bone marrow, a key part of clonal selection
What are the antigen-independent in B cell development?
occurs in the bone marrow during maturation.
What are the antigen-dependent phases
Occurs in peripheral lymphoid organs, where B cells differentiate after encountering an antigen.
What is shown in the maturation phase of the B cell development diagram?
transition from stem cell to mature naïve B cell, which is antigen-independent and occurs in the bone marrow.
What is the differentiation phase in B cell development?
antigen-dependent and occurs in the secondary lymphoid organs, where activated mature B cells become either antibody-secreting plasma cells or memory B cells.
Why is diversity in antigen receptors crucial for B cells?
BCR must recognize a vast array of potential antigens, so genetic rearrangements create a diverse pool of BCRs, each with a different specificity.
What is clonal deletion in the context of B cell development?
Clonal deletion is the process by which potentially self-reactive pre-B cells are removed to prevent the immune system from attacking the body’s own tissues.
What is clonal deletion in the context of B cell development?
process by which potentially self-reactive pre-B cells are removed to prevent the immune system from attacking the body’s own tissues.
When do specific immature B cells proliferate and differentiate?
Upon encountering their specific antigen and receiving necessary co-stimulatory signals, activated specific immature B cells proliferate and differentiate into effector cells.
What is the role of memory B cells?
persist after an antigen has been eliminated, providing a quicker and more robust response upon re-exposure to the same antigen.
What is the purpose of genetic rearrangement in B cells?
ensures that each B cell has a unique receptor, contributing to the immune system’s ability to recognize an immense variety of antigens.
How is the specificity of B cell receptors (BCRs) determined?
specificity of BCRs is defined by genetic rearrangements that occur during B cell development in the bone marrow.
What are the two main processes in B cell development?
maturation phase where B cells achieve immunocompetence, and differentiation phase where they become specialized effector cells.
What triggers the activation of naïve B cells?
when their receptors bind to a specific antigen and they receive co-stimulatory signals, leading to their proliferation and differentiation
SLO
secondary lymphoid organ
what is the maturation phase characterized by
CD45R
What happens to naive B cells upon encountering an antigen?
enter the antigen-dependent phase (activation and differentiation), where they interact with T helper cells in peripheral lymphoid organs.
What are the possible outcomes for an activated B cell?
undergo class switching, affinity maturation, become plasma cells secreting antibodies, or develop into memory B cells.
What processes enhance B cell effectiveness?
Class switching changes the antibody isotype produced, and affinity maturation increases the antibody’s ability to bind to the antigen.
What percentage of activated B cells survive to become effector cells?
10% survive, with the majority (~90%) undergoing cell death if they do not successfully undergo class switching or affinity maturation.
What is the role of memory B cells after the elimination of an antigen?
provide long-term immunity by responding more quickly and effectively upon re-exposure to the same antigen.
What are the stages of B cell development in the bone marrow?
Stem cell, early pro-B cell, late pro-B cell, large pre-B cell, small pre-B cell, immature B cell.
What marks the successful development of B cells in the bone marrow?
The successful generation of functional B cell receptor (BCR) expression, specifically IgM.
The successful generation of functional B cell receptor (BCR) expression, specifically IgM.
Heavy chain (H-chain) and Light chain (L-chain) bonded together by disulfide bridges.
What are the two types of regions found in H-chains and L-chains?
Constant region and variable region
Constant region on H and L-chains
determines the antibody subclass
Variable region on H and L-chains
determines antigen-binding affinity
Describe the heavy chain loci
V, D, and J gene segments
Describe the light chain loci
κ locus includes V and J segments, and the λ locus has multiple V and J segments.
What is the V(D)J rearrangement process in B cells?
process of somatic recombination that creates the variable region of the immunoglobulin heavy and light chains, generating the unique antigen-binding site of each B cell’s receptor.
What happens during the D-J rearranging stage of B cell development?
DJ, gene segments of the heavy chain (H-chain) undergo recombination. This is the first step in the variable region gene rearrangement.
What is the V-DJ rearranging step in B cell development?
Following D-J recombination, a V gene segment is joined to the D-J complex in the late pro-B cell stage, completing the rearrangement for the heavy chain locus.
What indicates the completion of heavy chain rearrangement in B cell development?
successful VDJ recombination of the heavy chain genes is confirmed in the large pre-B cell stage, allowing for the expression of the μ chain as part of the pre-B cell receptor on the cell surface
After heavy chain rearrangement, what is the next step for the light chain genes?
light chain genes begin their rearrangement with the V to J joining in the small pre-B cell stage, preparing the light chains to pair with the heavy chain.
What completes the immunoglobulin light chain gene rearrangement?
completion of the VJ rearrangement allows for the full assembly of the light chain, which can then pair with the heavy chain to form a functional B cell receptor.
When is immunoglobulin first expressed on the B cell surface?
Once both heavy and light chain rearrangements are complete, the B cell receptor, primarily IgM, is expressed on the surface of the immature B cell, indicating readiness for antigen encounter.
Main IgG subclasses
IgA, IgG, IgM, IgE and IgD
IgD function
antigen receptor on B cells that have not been exposed to antigens.
IgE Function
Binds to allergens and triggers histamine release from mast cells and basophils, and is associated with allergy and defense against parasitic infections.
IgM
First antibody to be produced in response to an antigen, primary activator of the complement system.
IgA subclasses and functions
IgA1: (most abundant) found in various secretions such as saliva and tears.
IgA2: More resistant to proteases and predominant in mucosal areas like the gut.
IgG subclasses (1-2)
IgG1: Most abundant IgG subclass in serum, effective in opsonization and complement activation.
IgG2: Responds mainly to polysaccharide antigens.