T cell-Dependent B cell Responses

Question 1

In the lymph nodes, B cells reside in the .. and T cells reside in the ..

Answer 1

B follicles
T cell zone

• they stay in their zones unless a specific protein comes thru and allows them to interact

Question 2

explain the Tcell - B cell collaboration to activate B cells in response to a protein antigen

Answer 2

all happens in the lymph nodes

red triangle specific B cell in the B cell zone
black peptide specific T cell in the T cell zone

for ex: a protein antigen processed into peptides by a dendritic cell, one of them being a black peptide
black peptide goes onto surface of class II dc
goes into lymph node and activates Tcell that is specific for the peptide then proliferates, will produce higher levels of a chemokine receptor (CXCR5- which is normally found on B cells
so bc it expresses CXCR5 the Tcells migrate to the B cells
CD40 ligand on surface

at the same time B cells recognize a protein, take it up then express it on surface MCHII (CCR7- normally on T cell) so it migrates to T cells
also has CD40 on its surface

slow migration of B and T cell toward each other in the lymph due to the induction of chemokine receptors
CD40 ligand wacks B cell induces signaling which causes the B cell to proliferate – exansion and differentiation into plasma cells that secrete antibodies (usually IgM antibodies - low affinity)

in short:
B cell recognizes a B cell epitope (the protein)
T cell recognizes a peptide on an MCH class II molecule
migation toward each other
T cell activates the B cell- proliferation

Question 3

B cells primarily present antigens to ..

Answer 3

CD4+ T cells

Question 4

What are the primary antigen presenting cells that are necessary to initiate collaboration between T and B cells in the lymph node?

Answer 4

dendritic cells & b cells

Dendritic cells (DCs) present antigen to naive T cells, leading to the activation of the T cells and their differentiation into helper T cells. B cells themselves present antigen to the helper T cells (derived from naive T cells previously activated by DCs). Helper T cells that are specific for the peptide-MHC complexes presented by B cells then provide activating signals to the B cells.

Question 5

When B cell receptors are bound by antigen, signals are generated in the B cell so that it will express a certain molecule that promotes migration to the T cell zone of lymph nodes. What is the name of this molecule?

Answer 5

CCR7

Question 6

what final interaction between B and T cells generates biochemical signals inside the B cell that lead to various activation responses including proliferation and antibody production

Answer 6

T cell induces expression of CD40L on the T cell, which in turn binds to CD40 on the B cell

Question 7

What do T cells express on their surface to migrate towards B cells?

Answer 7

CXCR5 and CD40L

Question 8

B cells take up protein antigens that bind to their B cell receptor by ….. These antigens are processed into peptides inside the cell and displayed on MHC class II - leading to B- T cell collaboration

Answer 8

receptor mediated endocytosis

Question 9

• very impt for generation of useful antibodies that can eradicate infections
• only occur with protein antigens
• it requires t cells and b cell collaboration and occurs in response to protein antigen
• take place in secondary lymphoid organs
• leads to generation of high affinity antibodies and isotype switched antibodies such as IgG IgA and IgE
• It leads to the generation of long lived plasma cells and memory B cells

Answer 9

Germinal centers (GC) 
formation of GCs is also called G.C. reactions

Question 10

what is the main point of the GC reaction?

Answer 10

the b cell - t cell interaction to produce antibodies only will produce IgM usually which have low affinity. It is useful at first to fight antigen but there is a need to improve the antibody resonse. That is when GC reaction comes in to make better antibodies

Question 11

how does the G.C. reaction occur?

Answer 11

B cell - T cell collaboration is the same to get IgM antibodies. Then you have expression of CXCR5 on both b and t cell. T cell changes into a T follicular cell. The CXCR5 on both cells allow them to migrate into the B follicle in lymph node. In the follicle, B cell undergos huge proliferation - clonal expansion of B cells. The T follicular helper cells also proliferate but to a lower level.
Then a Follicular dendritic cell (FDC) also is present in the follicle - show antigens to B cells.
Germinal Center is the follicule filled with B cells, T follicular cells, and FDCs.
G.C. - produces HIGH affinity antibodies (IgG, IgE, IgA) (process is called antibody switching)
long lived plasma cell - making these antibodies
long lived memory B cells - not always producing antibody but they will upon reexposure

Question 12

The germinal center reaction generates new cell types from antigen specific B cells that have gained certain functions. What are these cells?

Answer 12

Long lived plasma cells and memory B cells

• Long-lived plasma cells exit the germinal centers and move to the bone marrow. The plasma cells stay in the bone marrow and secrete high affinity antibodies. These are distinct from the short-lived plasma cells that are generated early in an antigen response outside of the germinal center reaction. Memory B cells are another product of the germinal center reaction

Question 13

GC reactions:
mutations are induced in the variable regions of the Ig genes that make the variable region on recptors of B cells
mutations are induced by T follicular helper cell signals
leads to changes in antigen binding sites in each Ig clone
affinity could increase or decrease
FDCs present in the G.C. show the protein antigen to the different subclones of the Igs on B cells
depending on how tight they bind - they either get signal to survive or will die by apoptosis
survival ones produce long lived plasma cells that secrete high affinity antibodies and generation of memory B cells

Answer 13

G.C. reaction

Question 14

outcomes of G.C. reaction

Answer 14

• Antibody affinity for antigen increases.
• B cells differentiate into long-lived plasma cells that secrete antibodies.
• B cells differentiate into memory B cells that can generate more plasma cells.
• There is isotype switching at the immunoglobulin genes to create IgA, IgG, or IgE antibodies with the same antigen specificity as the original IgM

Question 15

What are the signals provided by TFH cells that promote germinal center-specific changes to B cells such as proliferation?

Answer 15

cytokines and CD40L

• TFH express CD40L, which initiates CD40 signaling in B cells. Moreover, they secrete specific cytokines that promote germinal center events.

Question 16

In response to certain TFH (follicular t cells) signals, B cells can undergo high rates of mutation in which region of Ig genes?

Answer 16

the variable regions of Ig heavy and light chain genes

mutations are induced in the variable regions by TFcells - leading to different antibodies with differnet antigen binding sites some with higher affinity

FDCs present the protein antigens to the antibodies to see if they bind well - if not apoptosis

Question 17

a change in the constant region of the heavy chain (mu swap for gamma heavy chain) of antibodies that leads to a change in function? what cell signals this?

Answer 17

isotype switching

• Follicular T cells signal for B cells to undergo isotype switching in the GC reaction
• Generation of different antibody isotypes contributes to effective immunity
• impt to have variety of isotypes (IgM, IgG, IgE etc. ) of antibodies to fight infections via neutralization, complement fixation, opsonization, and ADDC

Question 18

so in the GC you have a B cell that is usually making IgM antibody. This B cell making IgM can under go what to switch from IgM -> IgA, IgG, IgE?
it changes the constant region of the heavy chain, but not the VDJ section (variable region- same specificity)

Answer 18

Isotype switching

Question 19

Germinal Center T cells tell B cells to undergo isotype switching. Isotype switching alters the antibody … chain but does not affect antibody … for antigen

Answer 19

heavy
affinity

VDJ stays the same - so the antibody has the same affinity but has a new heavy chain
switch regions on the heavy chain get cut and rearranged during isotype switching
IgM-> IgG1

Question 20

Which antibody isotype efficiently activates complement?

Answer 20

IgM

Question 21

Which antibody isotype efficiently neutralizes protein function?

Answer 21

IgG and IgA

Question 22

Which antibody isotype is most likely to activate mast cells?

Answer 22

IgE

Question 23

What process changes the nucleotide sequence of the genes encoding a B cell receptor antigen binding site during an immune response to protein antigen?

Answer 23

somatic hypermutation

• somatic hypermutation and class switching occur during the germinal center reaction. Only somatic hypermutation contributes to changes in the B cell receptor antigen binding site

Question 24

Isotype class switching does NOT change the … for diferent antigens. All will have same .. for antigens as IgM.

Answer 24

Affinity