B cells Flashcards
Structure of an antibody
2 heavy chains
2 light chains
Heavy and light chains are identical= 2 identical antigen binding sites
What links 2 heavy chains together?
Disulfide bonds
What links a heavy chain to a light chain?
Disufide bond
What does it mean for the antibody if it has 2 identical antigen binding sites?
Can bind simultaneously to 2 identical antigens
Increases total strength of interaction (avidity)
Antibody can cross-link 2 antigens and bind to antigen much more stably
Single antigen binding site and antigen have high affinity
What is the name of membrane bound immunoglobulins?
BCRs
variable region of antibody
Antigen-binding region
Varies in different antibodies= bind to a different specific antigen
constant region of antibody
Bottom part of antibody
Does not vary
C region remains inserted into membrane of B cell
Function of BCR?
Recognise and bind to a specific antigen via V regions
Transmits a signal to activate B cell
B cell presents antigens= B APC MHC II
Becomes activated by T helper cell
Leads to clonal expansion and antibody production (by plasma cells)
What is a major histocompatibility complex?
Large cluster of genes that codes for MHC molecules
What are MHC molecules?
Transmembrane glycoproteins
Encoded by MHC
What does it mean that MHC molecules are highly polymorphic?
each type of MHC molecule occurs in different versions within population
Increases range of antigens that can be bound to MHC molecule
What are the 5 different classes(isotypes) of antibody?
IgM, IgD, Ig,G, IgA, IgE
Most abundant antibody?
IgG
Hinge region
At centre of Y shaped antibody
gives flexibility to allow antibody to bind to 2 antigens
What does the variable region determine?
The antigen binding site
What does the constant region determine?
Isotype
What part of BCR allows it to anchor itself into b B cell membrane?
Hydrophobic amino acid sequence of carboxy terminus
name of process that allows different Ig’s to be made
Class switching of B cell
Y shape of antibody
Fc region (constant region) 2 fab regions= variable region
IgG
High affinity and tightly binds to antigen
Crosses placenta to baby
Enhances phagocytosis of bacteria and viruses (opsonisation)
IgM
First antibody to be made by cells in an immune response
Pentameric- 5 antigen binding sites connected to 1 constant region
Pick up trace amounts of infection to mark for recognition by phagocytes
Activates complement system
First to be made in an immune response
Most commonly produced but in blood plasma IgG>IgM
IgA
Dimeric- joining chain and secretory protein
Secreted at mucosal sites
Inhibiting bacterial and viral adhesion to epithelial cells Neutralisation of bacterial toxins and virus
Main Ig found in breast milk
IgD
B cell receptor
Enhances mucosal homeostasis
Activates B cells
IgE
Parasites and allergies
Induces activation of mast cells and basophils
Found on mast cells- bind to antigen= histamine released
What does a B cell need to be activated?
- Antigen binding to BCR= MHC II APC
- Costimulation (e.g CD40) from a T helper cell
- Cytokines from T helper cell-stimulate class switching of antibodies e.g IL-4,IL-5,IL-13
What determines the antibody type when BCR is binded to T helper cell?
Cytokines the B cell receives from T helper cell Cytokines cause class switching of B cell
What antibodies does the cytokines IL-4 inhibit?
IgM
IgG3
IgG2a
What antiboides does cytokines IFN-Gamma inhibit (MEG)
IgM
IgE
IgG1
What antibodies do IL-4 induce?
IgG1
IgE
What antibodies does IFN-Gamma induce?
IgG3
IgG2a
3 main functions of antibody
- Opsonisation (IgG)
- Neutralisation (IgA, IgG)
- Complement activation (IgM, IgG)
Opsinisation (IgG)
Antibodies coat pathogen
Phagocytes come and bind to constant region via Fc receptor
so phagocyte binds to fc region of Ig
Phagocytosis
Neutralisation (IgA and IgG)
IgA and IgG bind to bacteria toxins and virus particles
Prevent them binding to receptors on cells and causing damage
Complement activation (IgM and IgG)
IgM and IgG bind to their antigen= activates complement system (C1q)
Membrane attack complex formed
What antibody activates mast cells?
IgE
Mast cell releases histamine
What antibody activates basophils?
IgD
Basophil activates antimicrobial and pro- inflammatory mechanisms (histamine/heparin/cytokines)
What antibody activates eosinophils?
IgE Release granules (histamine/heparin)= death of parasite
Which antibodies are important components of mucosal immunity?
IgA and IgD
Production of B cell in bone marrow
Progenitor B cell converted to Pre B cell
( by somatic recombination (VDJ recombo) of heavy chain)
Creates a functional heavy chain in large pre B cell
Heavy chain associates with light chain and Somatic recombination of Ig alpha-beta dimer= forms pre BCR (large pre B cell)
Small pre B cell= VJ rearrangement of Ig light chain= functional BCR and expressed igM on its surface
Immature B cell formed (express IgM on surface)
What happens once immature B cell in bone marrow is made?
Enters lymph node/spleen
In lymph node:
Enters cortex (many b cells there)
Mature B cell enters paracortex
Activated by T-helper cell or antigen on pathogen
Travels to germinal centre
Enter dark zone of GC first
Dark zone= mature B cells proliferate+ clonal expansion, somatic hypermutation of BCRs(increase specificity and affinity)
B cells (centroblasts) enter light zone
Light zone= B cell with disadvantaged mutation (bad BCR) are removed (by apoptosis)
B cells= differentiate- memory/plasma cells
B cells with good BCR mutation= CLASS SWITCHING
Class switching- can convert IgM to IgA/G/E
Life cycle of B cell
Progenitor lymphoid cell (made from stem cell in bone marrow)
Progenitor B cell
(Heavy chain arrangement by somatic recombo-VDJ recombo)
Precursor B cell
(Light chain rearrangement by somatic recombo-VJ recombo)
Immature B cell (normally has IgM)
VDJ recombination(somatic recombination) of Heavy chain of BCR
BCR gene has= Variable region, Diversity region, joining region and constant region DJ recombination- J binds to D= brings C closer VDJ recombo Binds VDJ together Splicing- removes introns mRNA makes protein= HEAVY CHAIN Precursor B cell made THIS HAPPENS IN BONE MARROW
VJ recombination for light chain gene
Remember VDJ recombo of BCR happens in bone marrow
light chain gene= does NOT contain D segment
Light chain gene= V,J,C regions in DNA
VJ recombo- V and J bind to bring C c;loser
Splicing- introns removed
mRNA uses gene VJC to make light chain
Immature B cell made
THIS HAPPENS IN BONE MARROW
What can a progenitor lymphoid cell in bone marrow become?
Progenitor B cell
Progenitor T cell
What happens once immature B cell (IgM) is made in bone marrow when VDJ recombo is complete?
Immature B cell migrates to lymph node
becomes a mature B cell
Mature B cell enters dark zone of germinal centre in LN
In dark zone= somatic hypermutation of BCR gene(point mutation)= further increase specificity and affinity of antibody
Moves to light zone= class switching, B cell differentiates into memory/plasma cells
What are 2 ways in which a mature B cell can become activated?
- BCR binds to antigen on pathogen
- T helper cell activates B cell by T hElper cell binding to B cell APC (costimulation via CD40 and cytokines released by T helper= class switching of BCR)
How does antigen bind to antigen binding site of variable region of antibody?
Epitope of antigen makes contact with antigen binding site (variable region)
How does antibody (IgG) activate NK cells?
Antibodies (BCR) bind to epitope of antigen on surface of target cell
Fc receptors on NK cells recognise Fc region of antibody bound to antigen
Cross linking of Fc receptors on NK cells signals the NK cell to kill target cell
Activated NK cell kills target cell by apoptosis
How does antibody activate mast cells?
Plasma B cells secrete IgE
Fc receptors on mast cell binds to IgE
Mast cell coated with IgE
Antigen binding to igE cross links the antibody
Mast cells degranulate= release histamine
Inflammation
How does antibody (IgE) activate eosinophils?
Eosinophils recognise igE bound to parasites
Eosinophils release granules of histamine/heparin= killing parasite
In allergic and parasitic infections
How does antibody (Ig D) activate basophils?
Soluble IgD binds to basophils
Activates antimicrobial and proinflammatory mechanisms- cytokines/histamine
What cytokine induces IgA?
TGF-Beta/IL-21
Which cytokine induces IgG?
IFN-gamma
Which cytokine induces IgE?
IL-4
Which cytokine induces IgM?
IL-15
What happens once VDJ recombination of BCR is done in bone marrow?
B cells receive survival signals to leave bone marrow and enter lymph node- primary follicle
