L13, B cell development and activation

Question 1

B cells migrate from … to … during development

Answer 1

marrow to peripheral tissues

Question 2

B cell development begins where?

Answer 2

in the bone marrow

Question 3

what are the stages of B cell development in the bone marrow?

Answer 3

• starts from hematopoietic stem cells
• progressively differentiate into common lymphoid progenitors (CLPs) cells
• CLPs can give rise to either B cells or T cells
• the majority of CLPs that remain in the bone marrow eventually become B cells

Question 4

what two things do B cells express differently from one another during sequential development?

Answer 4

cell-surface receptors and adhesion molecules

Question 5

what signals are received from cell-surface receptors on developing B cells?

Answer 5

1. differentiation
2. proliferation
3. movement within the bone marrow environment

Question 6

where do B cells complete their differentiation?

Answer 6

the spleen

Question 7

how can stages of B cell development be defined?

Answer 7

by status of the BCR/Ig gene rearrangements and the expression of different markers

Question 8

when do developing B cells leave the bone marrow?

Answer 8

once they become Mature B cells

Question 9

What development occurs in the spleen?

Answer 9

mature B cell becomes activated via antigen stimulation, differentiation, IgM secreting plasma cells, class switching (becoming either memory B cells or Plasma cells secreting various isotyes)

Question 10

What happens in the early and late pro-B cell development?

Answer 10

• early pro-B cell stage: DJ recombination of the heavy chain
• late pro-B cell stage: V-DJ recombination of the heavy chain

Question 11

what happens in the large and small pre-B cell development?

Answer 11

• large pre-B cells express the pre-BCR
• small pre-B cell stage: V-J recombination of the light chain

Question 12

what are the 2 Pre-B cellcheckpoints

Answer 12

1. first checkpoint: functional pre-BCR (large pre-B)
2. second checkpoint: functional BCR and self-reactivity (Immature B)

Question 13

what is happening once developing B cells become immature B cells?

Answer 13

• express IgM at their surface and undergo negative selection
• leave the bone marrow towards the periphery and secondary lymphoid organs

Question 14

what are the three possible fates during negative selection of immature B cells?

Answer 14

1. deletion of autoreactive immature B cells
2. anergic
3. receptor editing

Question 15

what are the three possible fates of negative selection known as?

Answer 15

central tolerance

Question 16

what can the stages of B cell development be defined by?

Answer 16

• status of the BCR/Ig gene rearrangements
• expression of surface markers, notably:
  B220, CD19, Il-7R

Question 17

apart from differentiation, once in the spleen, immature B cells undergo what?

Answer 17

positive and negative selection

Question 18

what are transitional B cells?

Answer 18

B cells undergoing either positive or negative selection

Question 19

where do T1 transitional B cells undergo selection?

Answer 19

the periarteriolar lymphoid sheath (PALS)

Question 20

BCR with high affinity for self-antigens = …

Answer 20

negative selection

Question 21

where do T1 differentiate into T2?

Answer 21

in the follicle

Question 22

what kind of selection do T2 B cells undergo?

Answer 22

positive selection

Question 23

positive selection of T2 B-cells depends on what two survival signals?

Answer 23

• tonic signaling through the BCR
• binding of BAFF through a receptor

Question 24

what do mature B cells express on their surface?

Answer 24

both IgM and IgD

Question 25

what are the key differences between T cell and B cell development?

Answer 25

1. development of B cells does not involve the thymus
2. negative selection of B cells does not involve the expression of self-antigens in the thymus and does not involve recognition of MHC/self peptide…but both B cells and T cells bearing a self-reactive receptor are eliminated

Question 26

what is T cell dependent activation?

Answer 26

• an antigen binds to the BCR, is internalized, and is processed to be presented to Th cells
• co-stimulatory molecules strengthen the interactions between B and T cells
• Th cells secrete cytokines that further activate B cells

Question 27

What is T cell independent activation 1?

Answer 27

antigen binds to the BCR and others to PRR (ex. TLR)

Question 28

what is T cell independent activation 2?

Answer 28

antigen bound to the complement protein C3d interacts with the BCR and CD21 molecules

Question 29

what are the lymphoid organ regions?

Answer 29

T cell zone and Germinal center

Question 30

what occurs in the T-cell zone?

Answer 30

conventional naive B cell undergoes TD antigen activation and differentiates into memory or plasma cells

Question 31

what occurs in the Germinal Center?

Answer 31

• proliferation and somatic hypermutation in the dark zone
• selection of high-affinity, mutated, receptor-bearing B cells in the light zone

Question 32

what initiates somatic hypermutation?

Answer 32

enzyme AID (activation-induced cytidine deaminase)

Question 33

where do SHM occur in B cells? why are somatic hypermutations important?

Answer 33

in the variable regions of antibody-coding genes
important because they help fine-tune the binding affinity, a process called affinity maturation

Question 34

where does class switching recombination (CSR) occur?

Answer 34

in the germinal centers after T cell-dependent antigen stimulation

Question 35

in what region of the antibody genes does CSR occur in?

Answer 35

only the constant region