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Bcell Development


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What are the 3 phases of Bcell development?
1. Maturation
2. Activation
3. Differentiation
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.

-Negative selection
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


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
-Class switching
-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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