B Cells Flashcards
What are the 4 main effector functions of antibodies?
1-B Cell receptors
2-Neutralization
3-Opsonization
4-Signaling
*theoretic 1 x 10^16 and practical 1 x 10^9 diversity
What are the 3 main sources of diversity for antibodies?
1-Genetic diversity
2-Juncitonal diversity
3-Somatic hypermutation
What are the 5 antibody isotypes?
1-IgG (y) 2-IgM (u) 3-IgD (δ) 4-IgA (a) 5-IgE (ε)
What are the two main multimeric complexes?
1-Pentameric IgM
2-Dimeric IgA
*both contain J chains
Which isotype primarily functions to activate complement system but also transports across epithelium and neutralizes?
IgM
Which Isotype functions to sensitize basophils?
IgD
Which isotype primarily functions to neutralize, opsonize, activate complement, transport across placenta, diffusion into extravascular sites and also sensitizes mast cells and NK cells?
IgG
*IgG1, IgG2, IgG3, IgG4 in this category
Which isotype primarily functions to neutralize, transport across epithelium (dimer), diffuse into extravascular site (monomer) and also can activate complement and opsonization?
IgA
Which isotype primarily functions to sensitize mast cells but can sensitize basophils as well as diffuse into extravascular sites
IgE
Gene rearrangement happens in the _______ while somatic hypermutation and isotype switching happens in __________
Bone marrow, secondary lymphoid organs and circulation
What determines the antibody class?
Heavy chain
*Interacts with antigen and well as receptor, proportionally small variable region
What part of the antibody binds antigen, has proportionally large variable region and two isotypes (κ, λ)?
Light chain
The antigen binding region is called the _____ region and crystallizable/constant region is called_______?
Fab, Fc
What are 4 antibody antigen epitopes?
1-Terminal polysaccharide
2-Polysaccharide chain
3-globular protein surface
4-globular protein pocket
*can be linear, discontinues, multivalent
What creates antibody coding sequence?
Somatic recombination
What complex recognizes 7 or 9 bp recombination signal sequences to randomly pair gene segments in B cells?
RAG complex
After RAG cleaves the heptameter RSS and forms the D and J gene segments and opens the DNA hairpins, what enzyme adds the N-nucleotide segment to form the coding joint?
TdT- Terminal deoxynucleotidyl transferase
Though IgM is first expressed and then IgD, which antibodies can B cells express?
All types, however the isotype switch is permanent. They can be membrane bound or soluble as well
*express IgM/IgD until activated
Which 5 changes in immunoglobulin genes during B cell life are irreversible?
1-V-region assembly from gene fragments 2-Generation of junctional diversity 3-Assembly of transcriptional controlling elements 4-Somatic Hypermutation 5-Isotype switching
Which two changes in immunoglobulin genes during a B cells life are reversible and regulated?
1-Transcription activated with coexpression of surface IgM and IgD
2-Synthesis changes from membrane Ig to secreted antibody
Multiple antibodies targeted against the same antigen is called what?
Polyclonal
A single antibody targeted against a single antigen is called what?
Monoclonal
What are three diagnostic uses for antibodies?
1-Pathogen identification
2-Protein quantification
3-Cellular identification
What are 3 therapeutic uses for antibodies?
1-Targeted killing
2-Chemical delivery
3-Immunomodulatory
Antibodies bind _______ epitope but may bind _______antigens
One, Many
Strength of physical interaction between antibody and epitope is called?
Affinity
Overall strength of antigen binding is called?
Avidity
Which CD is present in a pluripotent hematopoietic stem cell?
CD 34
Which CD activates common lymphoid progenitor cells?
CD 10
Which CD activates B-cell precursor cells?
CD 127 (is an IL-7a receptor)
Which CD activates Pro-B cells?
CD 19 (is an A B cell co-receptor)
Where are the two checkpoints in B cell development?
1-Between Late Pro-B cell and Large Pre-B cell
2-Between Small Pre-B and immature B cell
During the Pro-B cell stages there is ______ immunoglobulin, during Pre-B cell stages there is _________ and in immature B cell stage there is ___________ immunoglobulin
No, Heavy chain, Functional
What cells do B cells interact with in bone marrow during development?
Stromal cells
Which three adhesion/signaling molecules are present in the Lymphoid progenitor cell with stromal cells?
- CAMs
- VLA-4
- VCAM-1
Which two adhesion/signaling molecules are present in the Early pro-B cell interaction with stromal cells?
- Kit
- SCF
*Turn on RAGs
Which main signaling molecule is present in the late pro-B cell interaction with stromal cells?
IL-7 receptor interacting with IL-7
Which two adhesion/signaling molecules are present in the pre-B cell interaction with stromal cells?
- CAMs
- IL-7
D-J rearrangements on both chromosomes for the heavy-chain gene are always productive and take place during which stage?
Early Pro-B cell stage
V-DJ rearrangement on the first chromosome for the heavy chain either survives or moves on to the second chromosome during which stage?
Late pro-B cell
50% of B cells survive
Pre-B cell receptor expression is the _______ checkpoint in B cell maturation
First
IgB stops RAGS, degrades heavy chain RAG complexes, changes heavy chain chromatin, and drives what?
Allelic exclusion
Expressed in the ER, which receptor is key in determining heavy chain requirements and works with Iga and IgB signaling components?
Pre-B cell receptor
What 3 things happen between Large and small Pre-B cell stages?
1-100 small Pre-B cells
2-RAG genes reactivated
3-Unique recombination per cell
What is the order of the four chances of product rearrangement or Light chain genes in Pre-B cells?
1-k gene on first chromosome
2-k gene on second chromosome
3-λ gene on first chromosome
4-λ gene on second chromosome
Which growth factor receptor is active during early pro-B cell stage and the beginning of late pro-B cell stage?
Kit
Which growth factor receptor is active during early pro-B cell stage until the end of Large pre-B cell stage?
IL-7 receptor
Which lymphoid-specific recombinases are active during late pro-B cell and Large Pre-B cell stages then turns off and is active again during Small Pre-B cell and immature B cells stages?
RAG-1 and -2
Which surrogate light chain component is active during early pro-B cell until the Small Pre-B cell stages?
λ5 and VpreB
What is the order of the 7 B cell maturity stages?
1-Stem cell 2-Early Pro-B cell 3-Late Pro-B cell 4-Large Pre-B cell 5-Small Pre-B cell 6-Immature B cell 7-Mature B cell
Which signal transduction proteins are active beginning in the early Pro-B cell stage all through Mature B cell?
Iga and IgB
Which signal transduction protein is active from the end of early pro-B cell until the beginning of Mature B cell stages?
CD19 (is a B cell co-receptor)
Exposure to self antigen, ensuring tolerance is called what?
negative selection
What are the two types of tolerance?
- Central tolerance (in bone marrow)
- Peripheral tolerance (peripheral organs/lymph nodes)
What are the three fates of strong binding in negative selection for antibodies?
1-Light chain reorganization
2-Apoptosis (if receptor is self-reactive)
3-Anergy (signaled to make IgD and becomes non-responsive)
What are three secondary lymphoid tissues?
1-Spleen
2-Lymph nodes
3-GALT
B cells enter a lymph node through what?
High endothelial venule
What attracts immature B cells to HEV?
Chemokine CCL21
CCL21 and which other chemokine attracts B cells into the lymph node?
CCL19
Which chemokine attracts B cells into the primary follicle?
CXCL13
Interaction with follicular dendrite cells and cytokines drive what?
Maturation of immature B cells
What are the 4 stages of B cell activation in lymphoid tissue?
1-Antigen exposure in cortex
2-Interaction with T cells (T-cell area)
3-Migration, secondary lymphoid follicle formation and clonal expansion (in germinal center)
4-Plasma cell production and antibody secretion
Dysfunctional B cells can cause what?
Cancer
