breakout 5

Question 1

How does a T-dependent Ab response occur in vivo?

Answer 1

Antigen-binding B cells are trapped in the T-cell zone of spleen
Antigen-binding B cells interact with armed helper T cells and begin to divide
B and T cells migrate to T zone (red pulp border) where they proliferate to form primary focus and form plasmablasts
Some B cells migrate to the B cell zones where they form the germinal center

Question 2

What aspects of a B cell: T cell interaction are required for a productive interaction and ultimately for Germinal Center formation?

Answer 2

MHC Class II (B cell) : TCR (T cell) interaction
CD40 (B cell) : CD154/CD40L (T cell)
B7 (CD80/86 on B cell) : CD28 (T cell)

Question 3

what is germinal center?

Answer 3

Anatomical site of intense B cell proliferatiokn, selection, maturation and death during an antibody response

Question 4

T cell zone:

Answer 4

T cell dependent activation

Question 5

light zone of germinal centre

Answer 5

proliferation slows down and become non-dividing; B cells increase expression of surface immunoglobulin and are called centrocytes; class switch recomb, affinity maturation, and memory B cell or plasma cell differentiation occur here

Question 6

dark zone of germinal center

Answer 6

site of massive B cell proliferation; B cells downregulate surface immunologbulin and are called centroblasts and somatic hypermutation occurs here and clonal expansion

Question 7

How does somatic hypermutation occur?

Answer 7

Random mutagenesis that is limited to VDJ regions and occurs only in mature, Ag-activated B cells (centroblasts) in germinal center
These mutations require: Transcription and Cis-acting elements
Increases affinity

Question 8

How does selection occur?

Answer 8

Light zone;
BCR signaling induces anti-apoptotic factors that protect cells from death
Competition for limiting amount of antigen at the end of immune response
- Only Abs that can compete for binding will give necessary survival signals to B cell
- Only B cells that can bind and internalize antigen will get the T cell help they need in the GC to survive

Question 9

Class switching

Answer 9

Result of cytokines informing the B cell to undergo isotype or class switching on the constant region
Differnet antibody isotypes provide different functions to the immunoglobulins
Increases function

Question 10

Differentiation

Answer 10

Plasma cell will produce lots of antibodies
Memory cells are long-lived and are important for quickly responding to antigens during later encounters
Increase immune response and memory

Question 11

Is there a dark side to a GC reaction?

Answer 11

• Many B cell lymphomas are derived from GC B cells
• Due to high rates of proliferation and induction of DNA damage
• They also downregualte apoptotic signals
• Genome instability: Class switch recombination and Somatic hypermutation

Question 12

GC rxn genes that are inappropriately expressed in cancer

Answer 12

BCL-6 PAX5: Block of differentiation and unlimited cell division
BCL-2 NF-kB: Prevention of apoptosis
c-MYC: Uncontrolled proliferation