Lecture 10 - B Cell Immunity Flashcards
How to THF cells help B cells make antibody and isotype switching? What to note? What is this called?
- T-follicular helper cell moves toward the B cell follicle under the influence of cytokines to the junction between T-cells and B-cell zone in the lymphoid tissue => TFH cell waits for a naïve B cell to come that has taken up an antigen in the B cell follicle
- B cell processes the antigen through the endocytic pathway, and as APC, it displays the antigen with MHC class II => B cell waits to meet with T-cell that has the same specificity for the peptide
- T-follicular helper cell binds MHC on B-cell => expression of CD40 ligand on T-cell (co-stimulatory molecule that help this interaction)
- T follicular helper cell then releases cytokines: IL-4, IL-5, IL-6, to the B cell which causes:
(1) B cell to proliferate and differentiate into antibody-secreting plasma cells (or memory cells), and
(2) determination of type of antibodies to make
NOTE: B cell and follicular helper T cell MUST recognize epitopes of the same antigen in order to interact BUT the B cell receptor doesn’t have to have that same peptide specificity as long as the MHC loaded peptide is the same as the one the DC presented to the TFH cell = linked recognition
Purpose of linked recognition between B cells and TFH cells?
Single TFH cell can activate B cells with different epitope BCR specificities
How do B cells become plasma cells? What happens to them?
B cells in germinal center proliferate
At first, these plasma cells may produce antibodies in the lymph node, but they will travel to bone marrow and continue to secrete antibodies from there
How are opsonized antigens in secondary lymphoid tissues loaded to B cells? 4 steps.
- Opsonized antigen enters the lymph node through the afferent lymphatic vessel
- Antigens bind to the CR1 and CR2 receptor (complement receptors 1 and 2) on the surface of the subcapsular sinus macrophages
- Follicular B cells come out and pick up the antigen from the surface of the macrophage using BCR
4a. B cells are then able to transport the antigen into the follicle, where it can be trapped on the surfaces of follicular dendritic cells in germinal centers
OR
4b. B cell takes up the antigen and processes it through the endocytic pathway => loads peptides through MHC II => goes to the junction of the B cell follicle and paracortex where the B cells will interact with T cells that have the correct specificity
Why are SCS macrophages capable of displaying antigens on their surfaces?
Because they are poorly endocytotic and have reduced levels of lysosomal enzymes compared with macrophages in the medulla
What kind of antigens can the follicular dendritic cells bind? Purpose?
- Complement receptor CR2: any antigen that activates the complement cascade
- Fcγ receptor for IgG: antigen-bound antibodies
Purpose: display antigens for naive B cells to be activated
Relevance of CR2 on the surface of the subcapsular sinus macrophages also being part of the B-cell co-receptor complex?
By using the complement receptor and BCR together, sensitivity for B cell signaling increases 10,000x because CR2 has specificity for antigen bound to C3, C3b, C3dg, so a complement-coated antigen can bind to both the complement receptor and BCR => bringing these together makes the B cell more sensitive
SPLEEN vs LYMPH NODE
THEORY 1 vs THEORY 2
SPLEEN: Theory 1
- Primary focus: marginal zone => IgM produced
- Secondary focus: B cells travel from primary focus to secondary focus (germinal center) alone where somatic hypermutations occur and class switching (T cells are obviously needed)
LYMPH NODE: Theory 2
- Primary focus: cognate pairs of antigen-activated B cells and helper T cells are formed in the T-cell zone and they travel to medullary cords (primary focus) => IgM short-lived
- Secondary focus: B and T cells travel together to germinal center where somatic hypermutations and class switching occurs (T cells are obviously needed)
How to follicular DCs display immune complexes?
On their dendrites
What are plasmablasts?
Immature plasma cells
Describe somatic hypermutation in B cells under the influence of FHT cells. Goal?
In the germinal center, rounds of point mutations and selection occur on the variable domain of the heavy and light chains of BCR under the influence of the helper T cell
Goal = to improve the fit of the paratope for the epitope to have stronger binding => resulting in high-affinity antibody-secreting plasma cells and high-affinity memory B cells
Where do the point mutations occur during hypermutation of BCRs? 3 names
CDRs = compliment determining regions mainly
= hyper-variable regions
= Ig V regions
When does somatic hypermutation of BCRs occur?
EVERY time the immune system fights a pathogen
Does somatic hypermutation occur in memory B cells? Why/why not?
YUP - to continue to improve affinity
What are the 3 possible outcomes of the point mutations during hypermutation of BCRs? Which 2 are most common?
- ***Point mutation makes no difference in antigen recognition
- ***Point mutation makes antigen recognition worse (e.g. in framework regions, which destroys the architecture of the variable domain)
- Point mutation makes antigen recognition better by having greater affinity for the epitope = affinity maturation
What happens to the B cells that undergo affinity maturation during hypermutation of BCRs?
These cells are going to have the advantage binding to antigens because they have higher affinity binding => B-cell proliferation and maturation to memory B cell or plasma cell
What happens to the B cells that have worse or identical affinity after hypermutation of BCRs?
Cells will not be able to bind to antigens as well and will be outcompeted leading to apoptosis
What triggers somatic hypermutation of BCRs?
Cytokines released by TFH cells
Is the generation of 2° antibody responses from memory B cells distinct from the generation of the primary antibody response? How? Overall? What to note?
YUP
- Secondary response has a 10–100-fold increase in the frequency of activatable B cells after priming/Primary response has lower frequency of antigen-specific B cells with a range of affinities for the antigen from diverse population of B cells
- Primary response has lower affinity for the antigen
- Primary response has a low rate of somatic hypermutations
- Primary response has IgM>IgG/Secondary response has more IgG and IgA thanks to isotype switching
Overall: the quality of the antibody response is radically altered in the secondary response, in that these precursors induce a far more intense and effective response
Note: differences amplified in tertiary response
