B cell lecture 2 Flashcards
B cell development and maturation
Pro B cell -> Pre-B cell -> Immature B cell
(Mature VDJ is complete)
B lymphocyte development in the periphery
Mature B cell
-> antigen stimulation
Activated B cell
->Differentiation
->IgM secreting plasma cells -> IgM Plasma cells secreting various isotypes
Memory B cells of various isotypes
IgG IgA IgE
B cell activation
By Helper T cell that respond to same antigen
2 types of B cell activation
Thymus Dependent
Thymus independent
Thymus dependent
T helper cell
Thymus independent
No T helper cell required
Thymus independent antigen mechanism
No T cell required
BCR complimentary antigen
Secondary antigen from same pathogen
Second signal
B cell activated
IgM
Thymus dependent antigen
BCR binds to antigen
Antigen internalised presented on MHC class II molecules
Helper T cell recognise MHC II through TCR
Release cytokines
B cell release antigen specific antibodies
Thymus dependent antigen B cell proliferation is facilitated by
CD4OL
IL4
What cytokine drives plasma cell
IL5
IL6
Where does B cell proliferation occur?
Germinal centres of the lymph nodes
Why do B cell become trapped temporarily?
T cell Zone
Contact with antigen + T helper cell
What is the germinal centres made up of?
Proliferating B cells
How many days after infection do B cell form?
7-10 days after an infection
What is the mantle zone?
Resting B cells displaced by activated B cells
What happens to B cells in germinal centre?
Somatic Hypermutation
Affinity maturation
Class Switching
Somatic Maturation
High antibody diversity
Point mutations V region -> light + heavy chain
Cystidine Deaminase
Intro nicks in the DNA that are repaired
Requires single strand of DNA
Targets DNA that is being transcribed Ig Genes
Affinity maturation
V region mutated, B cell selection based on ability to bind to antigen
Progression of somatic hypermutation antibodies become more specific
Summary affinity maturation
High affinity-> plasma cell -> antibody
-> memory cell
Low Affinity -> Cell Death
Clonal Selection
Antigenic Specificity
Antibody class switching
Early: IgM
DNA recombination
-> IgG IgA IgE
Different constant C region -> specific antigen binding region
How to generate specificity and diversity in bone marrow
Antigen independent
Pairing of different heavy and light chain
Recombination of V D J segments
Variability on the joins of the recombined gene segments
P and N region nucleotide addition
How to generate specificity and diversity in bone marrow in periphery
Antigen dependent
Somatic hypermutation
Class switching
Affinity maturation
Antibody functions
Neutralization
Opsonisation
Complement Activation
Neutralisation
Antibody binds to toxins released by bacteria
Block viral binding proteins
Block adherance of bacteria to host cells
Opsonisation
Phagocytosis by macrophages and neutrophil
Antibody subclasses: Distribution
Transport across epithelium
Mean Serum
Transport across Placenta
Diffusion into extravascular sites
Plasma cells controlled by?
BLIMP1
BLIMP 1
Switches off proliferation and
Affinity maturation
Memory Cells
Affinity maturation
Long lived
BCR: highly specific for an antigen
Do not secrete antibody
Antibody class switches
Courses of an infection
First antibody subclass
IgM
IgM expressed before
Before somatic hyperation
Multimer
10ag binding sites
IgG
Opsonises pathogens for phagocytosis
IgA
Epithelial
Neutralisation
IgE
Localises with mast cells
Mucosa
Vaccination
Memory immune response
Triggers formation of germinal centres: somatic hypermutation
Affinity maturation
Higher affinity antibodies produced
