Glossary of Bcell Development
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- What are the 3 phases of Bcell development?
- 1. Maturation
- Where does it occur:
- Maturation - in the bone marrow
Activ/Prolif - in peripheral lymphoid organs.
- Which phases are dependent or independent of antigen?
- Maturation - Ag independent
Acitvation/Proliferation - Ag dependent
- What takes place during Bcell maturation?
- -Immunoglobulin genes rearrange.
-Stromal cells assist Bcell progenitors into differentiating and proliferating into Mature B cells.
- What is Negative Bcell Selection?
- Clonal deletion of Bcells that have antibody to self-proteins IN THE BONE MARROW.
- How can self-reactive Bcells sneak out of being deleted?
- -Editing their light chains. There are two - lambda/kappa; replacing the self-reactive one can allow the B cell to survive.
- What type of a Bcell is prduced from maturation in the bone marrow?
- A mature naive Bcell that expresses only IgM on membrane; so far has never seen an antigen.
- What tells you if a Bcell is fully mature and ready to encounter Ag (without going into anergy)?
- if it has IgM and IgD both on membrane.
This shows that differential RNA processing and class switching has occurred.
- What occurs after mature Bcell exports from bone marrow?
-Where does it go
-What is it dependent on?
- Bcell activation/prolif/differentiation.
In the periphery
- What are the 2 routes Bcell activation can proceed by?
- -THYMUS dependent
- What's the difference between Thymus Dependent and Independent Ag activation?
- Thymus Dependent requires direct contact with Thelper cells secreting cytokines
thymus independent doesn't
- 2 types of Thymus-Independent Ag
- TI vs. T2
TI is LPS
T2 is repetitious polysaccaharide or flagella.
- What can LPS at high concentrations do?
- Activate polyclonal Bcells.
- What molecule similar to CD3 helps mIg become a Bcell receptor for activation?
- What is the purpose of the Iga/IgB molecule?
- Has intracellular ITAM motifs that can be phosphorylated to mediate signal transduction and Bcell activation
- how many signals are necessary for Bcell activation/proliferation?
- What are signals 1 and 2?
- 1. Cross-linking of the Bcell receptor by Antigen.
2. CD40 binds CD40-Ligand
3. Cytokines bind receptors
- What is the response to signal 1 -> cross-linking?
- ITAM of Iga/Igb is phosphorylated.
-Upregulates Class2 MHC and B7
-Allows Ag to present to Th cells, and Th cells can bind cuz B7 is there.
-Thelper cells then secrete CD40-L and cytokines.
- What is signal 2 for?
- CD40 binds CD40-L on Thelper cells.
This upregulates cytokine RECEPTORS on the B cell, so it can hear signal 3
- What is signal 3, and what is it for?
- Binding of cytokines to the receptors produced by signal 2.
Tells the Bcell to differentiate into memory cells, and which classes of Ig to switch to.
- Which signal starts Bcell proliferation?
- Signal 1.
- How are the signal requirements different between Thymus-dependent and Thymus-independent antigens?
- Thymus Independent crosslinks Bcells nonspecifically.
As a result, no requirement for
-CD40-CD40L signal #2 AND
-cytokine signal #3
Where all 3 are required for T-depnt Ag
- What 3 things are lacking in the Bcell response to Thymus-independent ag?
As a result, what type of population is activated?
- -No somatic hypermutation
-No affinity maturation
-No class switching.
Bcell population: POLYCLONAL, nonspecific.
- What are the differences between a primary and secondary humoral response?
- -Memory Bcells respond in a 2ndary
-Virgin naive cells do in a primary
-Mem Bcells take less time to proliferate/produce Abs; produce more Ab at peak, occurs sooner than for naive.
The Ab affinities in 2ary are higher than in primary.
-IgG predominates in 2'
-IgM predominates in primary.
- What is required of both Bcells and Th cells for a humoral response?
- both have to recognize epitopes on the same antigenic molecule.
- In peripheral lymphoid organs:
Where are naive b cells?
Where are naive T cells?
- Naive B cells are in cortex
Naive T cells are in paracortex.
- Where do B cells first encounter Ag?
- In primary follicles in secondary lymphoid tissue.
- What cells present Ag to B cells in primary follicles?
- Macrophages, B cells, and Dendritic cells.
- Where are primary lymphoid follicles located within 2ndary lymphoid tissue?
- in the paracortex.
- After initial Ag encounter by Bcells near the Tcell-rich paracortex, what happens?
- Some activated Bcells and Th cells migrate to Primary Follicles in center of spleen or wahtever 2ndary organ it is.
Allows maturation/selection with Follicular Dendritic cells.
- 3 important things that happen in Germinal Centers:
When is this?
- -Affinity maturation
-Generation of plasma/memory B cells.
about 7 days after initial activation.
- 2 ways you can regulate the immune response:
- -Antigenic competition (inject sheep RBC, then horse RBC will not cause as high of response cuz Sheep Ag takes up ab)
-Ab suppression (don't give infants some vaccines, because Maternal Ab to the Ag suppresses the humoral response generated).
- There are 2 Cytokines for which you must know how they affect class switching:
- 1.IL-4 causes IgE class switching (will result in allergies, type 1 hypersens)
2. IFN-y causes swithcing to Ig-G.
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