Adaptive Immune System: B-Cells Flashcards by Mary Doody

Lymphocytes in the central lymphoid tissues

Antigen independent differentiation

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Lymphocytes in the Peripheral lymphoid tissues

Antigen dependent differentiation

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The 8 important points about B-cells

Progenitor and immature are in the bone marrow or bursa fabricii in birds
Native Atg recognition (conformation epitop)
No MHC restriction
Secondary maturation occurs in the folliculi- this is stimulated by the Atg stimuli
The secondary maturation results in plasma cell or memory cell
Clonal B-Cell receptor
Cell-line marker: CD19+- is on every B-cell

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Evolution of B-Cells- locations

Bone marrow
Spleen (maturation)
Periphery

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Bone marrow: main functions

Production, maturation and differentiation of B-cells
One kind of specificity
Elimination of autoreactive cells
Transfer of useful B-cells to the periphery
Place of memory cells!

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Stages of development in the bone marrow

Signalled by the environment- bone marrow stroma cells
Pro B-Cell: earliest expression of CD19
Pre B-Cell: express rearranged heavy chain with Cmu chain and surrogate light chain
Immature B-Cell: expresses rearranged light chain (kappa mainly) and the membrane bound IgM (mIgM)

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Negative selection

The cell is capable of recognising the Atg when the heavy and light chain binds
The cells with high autoreactivity BCR should not enter circulation- they should be deleted
In the bone marrow, the autoreactive clones re-edit BCR with new recombination– receptor editing

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Spleen

Maturation of B-cells in the white pulp

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BAFF and APRIL

BAFF= B-Cell activating factor 
APRIL= proliferation-inducing factor- survival of B-cells

Functions:
Plasma cell survival
T-cell independent response and isotype switching
Immature B-cell survival and isotype switching

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Lymph Nodes: components and functions of the cortex

Primary follicle: B-cell activation
Secondary follicle germinal center: B-cell proliferation and maturation

Exclusively B-cells

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Lymph Nodes: components and functions of the paracortex

Initial T and B cell activation

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Lymph Nodes: components and functions of the medulla

Plasma cell secretion of antibody

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Important points about Follicular Dendritic Cells (FDC)

In the stratum germinativum of the secondary follicles
Myeloid progenitors
FcR and complement receptors (opsonisation)
Atg is held in a native form to B-memory cells
No phagocytotic activity
No expression of MHCII

*sidenote: remember Fc is part of IgG

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What are the 3 zones of the secondary follicle

Dark zone
Light zone
Mantle zone

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What happens in the dark zone?

The naive B-Cell undergoes clonal expansion and somatic hypermutation

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What happens in the light zone?

Desired: After the somatic hypermutation in the dark zone, the B-cell has improved affinity, undergoes selection and differentiation with FDC and T-cells
Cross-switching to become plasma cells and memory B cells

Undesired: Disadvantageous mutations leading to an apoptotic B cell

B-Cells as APC’s

Less Atg conc is effective 
Receptor mediated endocytosis 
1-6 hrs btw pathogen intake and presentation
The cells reproduce BCR within 8-24 hrs 
Conformation specific BCR (MHCII present linear Atg)
Presentation depends on: 
-CR2 (CD21) positive
-Fc gamma RIIb1 negative

What type of phase occurs in the bone marrow?

Antigen INDEPENDENT phase (maturation)

What type of phase occurs in the secondary lymphoid tissue?

Antigen DEPENDENT phase (activation and differentiation)

Affinity maturation
Isotype switch

Activation of naive B-cells

B cell presents Ag to Th by its BCR

In return, the Th gives the B cell CD40 and cytokines- the B-Cell is now activated

Somatic mutation and selection of B-Cells

Activation of B-cell and migration to centrum germinativum

Somatic Mutation:

Proliferation of B-Cell
Hypermutation of Ig’s V-gene

Selection:

Selection of high affinity Ig expressing B-cell
Apoptosis of B-Cells that do not recognise antigens

Migration of B-memory and high affinity Ig expressing B-Cell

What is the main function of plasma cells

Antibody secretion

What is the main function of IgG expressing B-cells

Isotype switching

What is the main function of high-affinity Ig expressing B-Cell

Affinity maturation (the connection btw Ag and Ab)
Memory B-Cell

Plasmablast can become

Long-lived plasma cell

BM: IgG MALT: IgA Red pulp in the spleen: IgM, IgG, IgA

Differentiation of activated B-Cells to plasma cells, what does it depend on?

Cytokines!! Prolif cytokines: IL- 2,4,5 Differentiation cytokines: IL-2,4,5 and IFNgamma and TGFbeta

IgG structure (6)

``` Most common in the blood (65-80%) Mw= 160,000 Bivalent monomer The gamma heavy chain is responsible for its subclasses Serum half life is 10-20 days Can cross the endothelium ```

IgG Functions (6)

``` Agglutination Precipitation Complement activation Neutralisation Opsonisatoin Cytotoxic reactions ```

IgM structure (8)

``` 5-15% of serum Ab's Mw= 900,000 Pentameric, disulphide bridges Its J chain has a Mr of 15,000 Mu heavy chain Pentavalent Serum half life is 5 days Usually does not cross the epithelium ```

IgM functions

``` Primary immune response BCR as monomer Agglutination Neutralisation Complement activation ```

IgA structure

``` 5-10% of serum abs NB ON BODY SURFACES!-- mucus membranes esp Mw=360,000 Dimeric (trimer or tetramer) but is mostly monomer in blood Has an alpha chain and a J chain Has secretory component (mucin) Half life in serum is 2 hours Half life on surfaces is 2 days Tetravalent ```

IgA Functions

Local immune response Agglutination Neutralisation Can migrate transcellularly

IgE structure

``` Less than 0.05% of serum Igs Mw= 200,000 Epsilon heavy chain Half life is 1-2 days Bivalent- can bind to metals and granulocytes ```

IgE functions

Type I hypersensitivity- anaphylaxis and allergy | Protozoa and parasite infections

IgD

``` BCR- is unstable Monomer Bivalent Mw= 180,000 alpha heavy chain half-life is 3 days Always on cell membranes ``` Sidenote from lecture: has a very long neck, the double chain can be destroyed therefore is not good in the blood!! is not physio found in the blood

Memory B-Cells...

Do not produce antibodies, but transform easily to plasma cells