Phases of B Cell Development

Question 1

What is hematopoiesis?

Answer 1

Constantly producing leukocytes. Older die by apoptosis, so constant numbers in circulation

Question 2

What is stage 1 of B cell development?

Answer 2

In marrow
lymphoid progenitor stimulated by stromal cells by direct contact and by secreted cytokines to become B cell
Ig gene rearrangement
negative selection

Question 3

What is stage 2 of B cell development?

Answer 3

In peripheral lymphoid tissue

B cells activated by Ag and then differentiate into Ab-secreting plasma cells

Question 4

What are the 6 phases of B cell development?

Answer 4

1. Repertoire assembly - make diverse and clonally expressed BCRs
2. Negative selection - alter, eliminate or inactivate BCRs that bind to self
3. Positive selection - promote selected immature B cells to mature in secondary lymphoid tissue
4. Search for infection - circulating mature B cells between lymph, blood and secondary lymphoid tissues
5. Find infection - activation and clonal expansion of B cells by Ags in secondary lymphoid tissue
6. Attack infection - differentiation to Ab-secreting plasma cells and memory B cells in secondary lymphoid tissue

Question 5

What occurs during repertoire assembly? NOT COMPLETE

Answer 5

Part of phase 1 in the marrow
B cell precursor (lymphoid progenitor) - interacts with stromal cells and cytokine secretions to become early proB cell - somatic recombination
Pro B cell - synthesis of mu heavy chain (gene rearrangement). If Ig nonfunctional, B cell can rearrange other allele, if unsuccessful then apoptosis, if successful then mu heavy chain goes on to next phase
Pre B cell - produce surrogate light chain with 2 subunits, VpreB and lambda S to test mu heavy chain
Pre B cell rearranges light chain

Question 6

How does mu heavy chain formation occur?

Answer 6

Early pro-B stage 1, heavy chain rearrangement is completed with one V region joining rearranged DJ
If rearranged Ig is nonfunctional, can try rearranging the other allele
If rearrangement fails, apoptosis
If rearrangement successful, mu heavy chain created

Question 7

How is a mu heavy chain tested?

Answer 7

Functionality is tested by being displayed as pre-BCR on pre-B cell
At this time, the heavy chain is associated with a surrogate light chain with 2 subunits: VpreB and lambda 5
Once a pre-BCR, signals to prevent more rearranging and other signals to proliferate with identical heavy chains and to start light chain rearrangement

Question 8

What is allelic exclusion?

Answer 8

Only one allele of Ig is expressed. One specificity per B cell, assuring high binding affinity

Question 9

How is the light chain formed in B cell development?

Answer 9

Pre-B cell ready to create the light chain
Kappa locus rearrangement attempted first. If not productive rearrangement on either kappa allele, will try lambda rearrangement
If unsuccessful, apoptosis

Question 10

What is negative selection?

Answer 10

Starts phase 2 in the marrow
Process of testing fully formed Ab for autoreactivity after random VDJ recombination
Pre B cells interact with adhesion molecules and surface signaling molecules
If pass the selection, will have formed and functional IgM BCR and will move to peripheral circulation and also start expressing IgD

Question 11

What is anergy?

Answer 11

Nonfunctioning.

Can be immature B cells that react with soluble Ag in the marrow and are short-lived in circulation. Die by apoptosis

Question 12

What happens during light chain editing?

Answer 12

Receptor editing - autoreactive B cell with marrow stromal cells get more chances to rearrange the light chain to become non-autoreactive

Question 13

What is the mu chain?

Answer 13

the IgM heavy chain

Question 14

Define clonal deletion

Answer 14

death of self-reactive cells

Question 15

Define central tolerance

Answer 15

immunological tolerance to self - unresponsiveness of immune system to self

Question 16

Define peripheral tolerance

Answer 16

Silencing of self-reactive B and T cells in the periphery