Lecture 32 - B cells VI

Question 1

What are the two main zones in the germinal center?

Answer 1

The dark zone and the light zone.

Question 2

Where are follicular helper T cells found in the germinal center?

Answer 2

Follicular helper T cells are found in the light zone of the germinal center.

Question 3

What role do follicular dendritic cells (FDCs) play in the germinal center?

Answer 3

FDCs retain antigen in the light zone for interaction with B cells.

Question 4

What happens in the germinal center?

Answer 4

The germinal center is dynamic and complex, where B cells undergo somatic hypermutation and class switching.

Question 5

What happens to B cells when they first enter the germinal center?

Answer 5

They have already encountered antigen (signal 1), been activated by T cells at the B-T border (signal 2), and proliferated. They can produce IgM/IgD with baseline affinity.

Question 6

What occurs in the germinal center related to somatic hypermutation?

Answer 6

Somatic hypermutation occurs in the germinal center, leading to an increase in antibody affinity for the antigen while maintaining antigen specificity.

Question 7

What happens during class switching in the germinal center?

Answer 7

Class switching replaces the IgM/IgD heavy chain with other isotypes like IgG, IgA, or IgE, while keeping the same antigen specificity.

Question 8

What is secondary diversification in the germinal center?

Answer 8

Secondary diversification occurs after B cells receive signal 1 and 2 again, involving somatic hypermutation (higher affinity for antigen) and class switching (changing isotype but maintaining specificity).

Question 9

How does somatic hypermutation affect B cells in the germinal center?

Answer 9

Somatic hypermutation improves the affinity of B cells for their antigen, while their antigen specificity remains the same.

Question 10

How does class switching work in the germinal center?

Answer 10

Class switching replaces one heavy chain constant region with a different isotype, such as IgG, IgA, or IgE.

Question 11

What happens to Ig genes during somatic hypermutation and class switching?

Answer 11

These processes act on already rearranged Ig genes, meaning V(D)J recombination has already occurred in the variable region and cannot be reversed.

Question 12

What is the primary role of the light zone in the germinal center?

Answer 12

The light zone is thought to be the primary site of plasma and memory cell differentiation.

Question 13

What occurs in the dark zone of the germinal center?

Answer 13

The dark zone is thought to be the site of somatic hypermutation, where B cells undergo mutation to improve affinity for the antigen.

Question 14

What is the role of follicular dendritic cells (FDCs) in the germinal center?

Answer 14

FDCs serve as an antigen concentration site for future selection and differentiation of B cells.

Question 15

How do follicular helper T cells (TFH) contribute to the germinal center?

Answer 15

TFH cells provide the necessary signals for B cell differentiation, memory cell production, and class switching.

Question 16

What happens to B cells in the dark zone of the germinal center?

Answer 16

B cells in the dark zone undergo somatic hypermutation, leading to cells with the same specificity but different affinity for the antigen.

Question 17

What happens when B cells from the dark zone migrate to the light zone?

Answer 17

B cells migrate to the light zone where they compete to bind antigen trapped on FDCs. Higher affinity B cells will bind the antigen and receive signal 1.

Question 18

What is affinity maturation?

Answer 18

Affinity maturation is the process that selects for B cells with higher affinity for the antigen, resulting in the survival of those cells.

Question 19

What happens to lower affinity B cells in the germinal center?

Answer 19

Lower affinity B cells fail to bind antigen, do not receive signal 1, and undergo apoptosis.

Question 20

How do B cells interact with TFH cells in the germinal center?

Answer 20

B cells that process and present antigen on MHC II interact with TFH cells via linked recognition. TFH cells provide a signal through CD40 (part of signal 2) and cytokines for class switching.

Question 21

How do cytokines from TFH cells affect B cells?

Answer 21

Cytokines from TFH cells instruct B cells on which antibody isotype to produce, resulting in class switching.

Question 22

What can happen to B cells after receiving signals from TFH cells?

Answer 22

B cells can re-enter the dark zone and undergo additional rounds of somatic hypermutation.

Question 23

What are the characteristics of plasma cells?

Answer 23

Plasma cells stop expressing high levels of BCR, secrete antibodies (IgG, IgA, IgE) of the same specificity as the progenitor B cell, and bind antigen with higher affinity.

Question 24

What are the characteristics of memory B cells?

Answer 24

Memory B cells express high levels of BCR with the same specificity as the progenitor B cell, and their BCR has a higher affinity for the antigen.

Question 25

What is the role of AID (Activation-Induced Cytidine Deaminase) in somatic hypermutation?

Answer 25

AID is responsible for deaminating cytidine residues in single-stranded DNA, converting cytidine to uridine, which is then removed.

Question 26

What happens when cytidine is deaminated during somatic hypermutation?

Answer 26

Cytidine is converted to uridine, which is then removed from the DNA.

Question 27

What role does the mismatch repair pathway play in somatic hypermutation?

Answer 27

The mismatch repair pathway, along with error-prone polymerase activity, inserts any nucleotide into the nick created by uridine removal, leading to point mutations.

Question 28

Where do point mutations occur during somatic hypermutation?

Answer 28

Point mutations occur in the heavy- and light-chain variable regions of immunoglobulins (Ig).

Question 29

What happens to some of the mutations produced during somatic hypermutation?

Answer 29

Some mutations result in nonproductive B cells that cannot bind antigen effectively.

Question 30

How does somatic hypermutation contribute to affinity maturation?

Answer 30

Somatic hypermutation generates mutations that select for B cells with higher affinity for the antigen, improving antibody binding and enhancing immune response.

Question 31

Where does somatic hypermutation mainly occur in immunoglobulins?

Answer 31

Somatic hypermutation mainly occurs in the complementarity-determining regions (CDR loops) of the variable regions.

Question 32

How do B cells with higher affinity for antigen survive in somatic hypermutation?

Answer 32

B cells that bind, process, and present more antigen to T cells for cytokine assistance survive, leading to affinity maturation.

Question 33

How does antibody affinity change with increased exposure to antigen?

Answer 33

With increased exposure, somatic hypermutation leads to increased antibody affinity for the antigen.

Question 34

When does class switch recombination (CSR) occur?

Answer 34

CSR occurs within the germinal center after antigen contact, following the second signal (Signal 2).

Question 35

What signals are required for class switch recombination (CSR)?

Answer 35

B cells must receive costimulatory signals from CD40 and a cytokine signal that determines the isotype to be produced.

Question 36

What does class switch recombination (CSR) select in the immune response?

Answer 36

CSR selects which heavy chain constant region will be produced, resulting in the production of a different antibody isotype.

Question 37

Where does recombination occur in class switch recombination?

Answer 37

Recombination occurs between switch regions: one after the VDJ region and one upstream of the constant region to be recombined.

Question 38

How is transcription activated in class switch recombination (CSR)?

Answer 38

When B cells receive a cytokine signal, transcription is activated upstream of the constant region.

Question 39

What is the role of AID (Activation-Induced Cytidine Deaminase) in class switch recombination (CSR)?

Answer 39

AID acts on single-stranded DNA (ssDNA) to initiate the process of class switch recombination by creating nicks in the DNA.

Question 40

What happens after double-stranded breaks (DSBs) are created in DNA during CSR?

Answer 40

The DSBs are repaired by the DNA repair machinery, which cuts out the intervening DNA and brings the selected constant region adjacent to the VDJ region.

Question 41

Is class switch recombination reversible?

Answer 41

No, class switch recombination is irreversible once the double-stranded breaks have occurred and the DNA has been recombined.

Question 42

How does the immune system handle early and late reinfections?

Answer 42

Early reinfection is handled by pre-formed antibodies and effector T cells from the primary response, while late reinfection is handled by immune memory B and T cells.

Question 43

What is immunological memory?

Answer 43

Immunological memory is the ability of the immune system to respond more rapidly and effectively upon re-exposure to an antigen, facilitated by adaptive immune mechanisms.

Question 44

What are the key features of immunological memory?

Answer 44

Immunological memory is antigen-specific, long-lived, and leads to a stronger immune response upon re-encounter with the pathogen, either through prior infection or vaccination.

Question 45

When do memory responses occur?

Answer 45

Memory responses occur after the primary response, typically in subsequent secondary and tertiary responses by lymphocytes generated late in the primary response.

Question 46

What are the differences between primary and memory immune responses?

Answer 46

Memory responses have more antibodies, more immune cells, higher affinity antibodies, and different lymphocyte features compared to the primary response.

Question 47

What are some key questions in the field of immunological memory?

Answer 47

What are the unique features of memory cells? How is memory maintained? When and how do memory cells arise? How are memory cells maintained over time?

Question 48

How is immunological memory detected in B cells and T cells?

Answer 48

Immunological memory is easier to detect in B cells as antibodies can be measured in serum, while memory T cells reside in tissues.

Question 49

What mediates immunological memory?

Answer 49

Immunological memory is mediated by a small and steady number of memory cells, some of which proliferate at any given time.