Lecture 32 - B cells VI Flashcards
What are the two main zones in the germinal center?
The dark zone and the light zone.
Where are follicular helper T cells found in the germinal center?
Follicular helper T cells are found in the light zone of the germinal center.
What role do follicular dendritic cells (FDCs) play in the germinal center?
FDCs retain antigen in the light zone for interaction with B cells.
What happens in the germinal center?
The germinal center is dynamic and complex, where B cells undergo somatic hypermutation and class switching.
What happens to B cells when they first enter the germinal center?
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.
What occurs in the germinal center related to somatic hypermutation?
Somatic hypermutation occurs in the germinal center, leading to an increase in antibody affinity for the antigen while maintaining antigen specificity.
What happens during class switching in the germinal center?
Class switching replaces the IgM/IgD heavy chain with other isotypes like IgG, IgA, or IgE, while keeping the same antigen specificity.
What is secondary diversification in the germinal center?
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).
How does somatic hypermutation affect B cells in the germinal center?
Somatic hypermutation improves the affinity of B cells for their antigen, while their antigen specificity remains the same.
How does class switching work in the germinal center?
Class switching replaces one heavy chain constant region with a different isotype, such as IgG, IgA, or IgE.
What happens to Ig genes during somatic hypermutation and class switching?
These processes act on already rearranged Ig genes, meaning V(D)J recombination has already occurred in the variable region and cannot be reversed.
What is the primary role of the light zone in the germinal center?
The light zone is thought to be the primary site of plasma and memory cell differentiation.
What occurs in the dark zone of the germinal center?
The dark zone is thought to be the site of somatic hypermutation, where B cells undergo mutation to improve affinity for the antigen.
What is the role of follicular dendritic cells (FDCs) in the germinal center?
FDCs serve as an antigen concentration site for future selection and differentiation of B cells.
How do follicular helper T cells (TFH) contribute to the germinal center?
TFH cells provide the necessary signals for B cell differentiation, memory cell production, and class switching.
What happens to B cells in the dark zone of the germinal center?
B cells in the dark zone undergo somatic hypermutation, leading to cells with the same specificity but different affinity for the antigen.
What happens when B cells from the dark zone migrate to the light zone?
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.
What is affinity maturation?
Affinity maturation is the process that selects for B cells with higher affinity for the antigen, resulting in the survival of those cells.
What happens to lower affinity B cells in the germinal center?
Lower affinity B cells fail to bind antigen, do not receive signal 1, and undergo apoptosis.
How do B cells interact with TFH cells in the germinal center?
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.
How do cytokines from TFH cells affect B cells?
Cytokines from TFH cells instruct B cells on which antibody isotype to produce, resulting in class switching.
What can happen to B cells after receiving signals from TFH cells?
B cells can re-enter the dark zone and undergo additional rounds of somatic hypermutation.
What are the characteristics of plasma cells?
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.
What are the characteristics of memory B cells?
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.
What is the role of AID (Activation-Induced Cytidine Deaminase) in somatic hypermutation?
AID is responsible for deaminating cytidine residues in single-stranded DNA, converting cytidine to uridine, which is then removed.
What happens when cytidine is deaminated during somatic hypermutation?
Cytidine is converted to uridine, which is then removed from the DNA.
What role does the mismatch repair pathway play in somatic hypermutation?
The mismatch repair pathway, along with error-prone polymerase activity, inserts any nucleotide into the nick created by uridine removal, leading to point mutations.
Where do point mutations occur during somatic hypermutation?
Point mutations occur in the heavy- and light-chain variable regions of immunoglobulins (Ig).
What happens to some of the mutations produced during somatic hypermutation?
Some mutations result in nonproductive B cells that cannot bind antigen effectively.
How does somatic hypermutation contribute to affinity maturation?
Somatic hypermutation generates mutations that select for B cells with higher affinity for the antigen, improving antibody binding and enhancing immune response.
Where does somatic hypermutation mainly occur in immunoglobulins?
Somatic hypermutation mainly occurs in the complementarity-determining regions (CDR loops) of the variable regions.
How do B cells with higher affinity for antigen survive in somatic hypermutation?
B cells that bind, process, and present more antigen to T cells for cytokine assistance survive, leading to affinity maturation.
How does antibody affinity change with increased exposure to antigen?
With increased exposure, somatic hypermutation leads to increased antibody affinity for the antigen.
When does class switch recombination (CSR) occur?
CSR occurs within the germinal center after antigen contact, following the second signal (Signal 2).
What signals are required for class switch recombination (CSR)?
B cells must receive costimulatory signals from CD40 and a cytokine signal that determines the isotype to be produced.
What does class switch recombination (CSR) select in the immune response?
CSR selects which heavy chain constant region will be produced, resulting in the production of a different antibody isotype.
Where does recombination occur in class switch recombination?
Recombination occurs between switch regions: one after the VDJ region and one upstream of the constant region to be recombined.
How is transcription activated in class switch recombination (CSR)?
When B cells receive a cytokine signal, transcription is activated upstream of the constant region.
What is the role of AID (Activation-Induced Cytidine Deaminase) in class switch recombination (CSR)?
AID acts on single-stranded DNA (ssDNA) to initiate the process of class switch recombination by creating nicks in the DNA.
What happens after double-stranded breaks (DSBs) are created in DNA during CSR?
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.
Is class switch recombination reversible?
No, class switch recombination is irreversible once the double-stranded breaks have occurred and the DNA has been recombined.
How does the immune system handle early and late reinfections?
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.
What is immunological memory?
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.
What are the key features of immunological memory?
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.
When do memory responses occur?
Memory responses occur after the primary response, typically in subsequent secondary and tertiary responses by lymphocytes generated late in the primary response.
What are the differences between primary and memory immune responses?
Memory responses have more antibodies, more immune cells, higher affinity antibodies, and different lymphocyte features compared to the primary response.
What are some key questions in the field of immunological memory?
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?
How is immunological memory detected in B cells and T cells?
Immunological memory is easier to detect in B cells as antibodies can be measured in serum, while memory T cells reside in tissues.
What mediates immunological memory?
Immunological memory is mediated by a small and steady number of memory cells, some of which proliferate at any given time.
