Lecture 18 - Concepts of B cell activation and Response to Infection

Question 1

Describe the two forms in which antibodies exist

Answer 1

As a membrane receptor (B cell receptor [BcR]) that binds antigen
As a secreted, fluid phase molecule that directs a specific immune function
1. complement fixation
2. opsonisation
3. neutralisation

Question 2

Describe B cell signalling

Answer 2

Co-receptors Iga Igb have tyrosine
kinase activity

Complement bound to pathogen can
also help target pathogen to BcR

CD19/CD81 form a co-receptor complex
that provides costimulatory amplification
of signals through the BcR

CD4+ T cell help vital for activation, and
differentiation of B cells into plasma cells

Question 3

How is the B cell shut down?

Answer 3

when B cell response no longer needed, the B cell is shut down by signals through the negative
regulator FcgRIIB
CD19, CD21 and CD81 act as ‘costimulatory signals’ for B cell activation
Mutations in FcyRIIB have been linked to autoimmune production of autoantibodies to host cells

Question 4

Explain the role of the germinal centre

Answer 4

This is where activation, proliferation and differentiation into plasma cell takes place - reason it is lighter is because only B cells with triggered antigen receptor are present there. Animals with mutation so that they have no germinal centre cannot carry out antibody responses
B cell triggered by antigen, moves into germinal centre
There is an interaction between activated B cell, follicular dendritic cell and helper T cell - work together to cause B cell to proliferate (+ somatic hypermutation and class-switch recombination)
3 possible fates for B cell: plasma cell, memory cell or death
There is a checkpoint in the germinal centre, similar to what happens in bone marrow - BCR is assessed for autoreactivity
In bone marrow it can be receptor edited but here if it is autoreactive it is just killed off

Question 5

What are CD4+ Follicular T helper cells?

Answer 5

These T cells are essential for formation and propagation of the germinal centre - present in the germinal centre telling B cell to proliferate, somatic hypermutate and class switch
Quite different from other varieties of T helper cell
Its transcription factor is Bcl-6, makes cytokine IL-21

Question 6

What is somatic hypermutation?

Answer 6

Activation induced deaminase (AID) is active in germinal centre to facilitate somatic hypermutation

• Mutations in the hypervariable region enable a tighter fit between the BcR and antigen
• Each subsequent encounter hones the antigen binding site further
• B cells that have undergone SHM will have their BcRs re-screened to determine if the mutations generated lead to an autoreactive BcR - if so the B cell dies

Question 7

Explain how class switching takes place

Answer 7

AID causes switch regions to form a hairpin loop that brings together the Fc constant regions to change.

Brings new Fc constant region to the VDJ region so specificity of the antibody stays the same