L6: B Cell Activation Flashcards
What can Abs secreted by plasma cells cause?
- neutraliation: prevents bacterial adherance
- opsonisation: promotes phagocytosis
- complement activation: activates complement which enhances opsonisation and lyses some bacteria
B cells only need 1 signal to become activated. True or false?
False, they need several signals
How is signal 1 in B cell activation triggered?
By the binding of Ag to BCR in secondary lymphoid tissue
What induces intracellular kinases?
BCR-associated polypeptides delivering a specific signal
What factors can increase/ decrease signal 1?
- if Ag has activated complement cascade
- lots of C3b
- by complement receptor 2 (CR2) on B cell surface (CD21)
- by CR2/ CD19/ CD81 forming the BCR co receptor complex
What affects how B cells recive signal 2?
The type of Ag they bind
- thymus independent (TI) Ag provides signal 2 either by the antigen itself or extensive cross linking of BCR
What are the 2 types of Ab production (only IgM) lead by TI Ag?
TI- 1 and TI-2 Ag
How do TI- I Ags cause Ab production?
TI- 1 Ag binds BCR and other receptors on B cell providing signal 2
- in [high] these Ag act as polyclonal activators (mitrogens) for B cells, activating many B cells irrespective of their BCR
- the 2 signals (from BCR and TLR) lead to B cell activation, proliferation and absecretion
How do TI-2 Ags cause Ab production?
TI-2 Ags contain repeated epitopes and will therefore cross-link many BCR molecules on the same B cell surfaces
- this takes longer (as more Ag required) to induce B cell activation
- Ab responses to TI-2 Ags typically don’t occur until >5yrs in humans
What type of cell does TD Ag require the presence of?
CD4+ T cells
How are TD Ags able to produce all classes of Abs?
- T cells activated by MHC/ peptide on APC
- BCR binds antigen triggering signal 1
- B cell internalises Ag, processes and presents Ag to CD4+ T cells triggering signal 2 via CD40/ CD40L interaction
- Cytokines secreted by T cell then help B cells to class switch
How do B cells ‘act as APC’ for TD Ag?
Epitopes recognised by Ab and T cell must be physically linked, either from different parts of the same molecule or from different molecules of complex
*How can B cells ‘acting as APC’ be used to improve the response to TI Ags?
- B cell binds bacterial polysacc (sugar) epitope linked to tetanus toxid protein
- Ag internalised and processed
- Peptides from protein componenet are presented to T cell
- Activated B cell produces Ab against polysacc Ag on surface of bacterium
These Abs can now class switch creating a conjugate vaccine
What is required for good Ab responses and why?
B/ CD4+ T cell interactions
- B cells enter lymph node from lood and comes into contact with specific Ag and can be activated
- If Ag is TD, B cells present peptide from Ag to CD4+ Th cells are boundary of T/B areas within the lymph node forming B/T cell conjugates
What happens as a result of B cells binding Ag via BCR and presenting peptide from Ag to CD4+ Th cell?
T cell then expresses CD40 ligand (CD40L) and secretes cytokines
What triggers B cell proliferation?
B cell receives signal 2 from T cell via CD40/ CD40L binding and via cytokine from T cell binding receptors
What other molecule can the CD40 signal induce
Activation induced deaminase (AID) which is required for class switching and somatic hypermutation
What are germline centres (GCs)
They are centres of increased proliferation formed in the B cell follicle
What occurs in GCs?
Cells divide rapidly to become centroblasts and undergo somatic hypermutation of Ig genes and isotype switching
When in GCs what are the 3 possible outcomes for B cells?
- differentiate into plasma cell, secreting various isotypes and high affinity Ab somatically mutated
- form long lived memory cells and recirculate
- die within lymphoid tissue
What is the main purpose of somatic hypermutation?
It introduces point mutations into V regions of Ig
- there’s ~1 mutation per V region/ cell division
- primarily involves AID and DNA repair genes
What other cell type is present in GCs and what is its function?
- Follicular dendritic cells (FDC) which aren’t bone marrow derived.
- They capture intact Ag for centrocytes to bind via BCR
- Oversees B cell affinity maturatino
Why do centrocytes compete with each other for Ag on FDC and signals from Tfh cells?
Centrocytes that undergo somatic hypermutation express mutated BCR on surface
How can mutated BCR receive a CD40 signal from Tfh cell?
If mutated BCR binds Ag on FDC better than unmutated BCR
What are Tfh cells (follicular T helper cells)
They are a CD4+ Th subset mainly found in B cells follicles in lymphocytes.
- specialised to provide help to B cells
- secreted by Th1/2 type cytokines
- can be identified with specific markers that difffers from other subsets of CD4 Th cells
How does the CD40 signal turn on somatic hypermutation
Through interactions with Tfh, protecting centrocytes from apoptosis and inducing isotype switching
- different cytokines induce different isotypes to be produced
