Immunology 5: B Lymphocytes

Question 1

What do the absence of T and B cells cause

Answer 1

Severe Combined Immune Deficiency (SCID)

Question 2

Where do B cells come from?

Answer 2

B cell generation and maturation occurs in bone marrow in the absence of antigen

They migrate into the circulation and into lymphoid tissues

Each B cells will recognise a specific antigen

Specificity resides in the BCR (B Cell Receptor) - this is a membrane-anchored antibody

Question 3

key difference between T cells and B cells in the TYPE OF EPITOPE they recognise:

Answer 3

T cells - identify the sequence

B cells - identify the structure (tertiary)

Question 4

What is the epitope

Answer 4

the region of an antigen that the antibody binds to

Question 5

What does the B-cell receptor look like

Answer 5

The B cell receptor is an antibody that is bound to a couple of transmembrane domains which transduce the signal.

Question 6

What does the BCR consist of

Answer 6

membrane-anchored antibody and di-sulphite linked heterodimers Iga and Igb

Question 7

What are the roles of the Igalpha and IgBeta hetrodimers

Answer 7

The cytoplasmic tails of Iga/Igb is long enough to interact with intracellular signalling molecules

When the BCR recognises an antigen, there is a structural change which drives signalling via Iga/Igb

Question 8

How are antigen receptors produced

Answer 8

Each BCR receptor chain is encoded by separate multigene families on different chromosomes

During B cell maturation these segments are rearranged and brought together

In essence, you produce a small number of building blocks which you can shuffle around and produce a lot of variety - happens in T and B cells

This is called IMMUNOGLOBULIN GENE REARRANGEMENT

This generates the diversity of the lymphocyte repertoire

Question 9

Describe the Expression of an Immunoglobulin Light Chain

Answer 9

There are 70 variable units that people have - 40 in kappa and 30 in lambda

The variable units exist in the genomic DNA in a cluster

B cells start in the bone marrow as immature B cells - they have germline DNA

As B cells develop, they get rid of most of the variable units and leave a few Variable and Joining regions (this is random)

So then the B cell has a variant version of this gene.

Different splicing patterns give rise to further variation

Question 10

What enzyme enables DNA recombination

Answer 10

V(D)J Recombinase

Encoded by RAG genes

Deficiency leads to SCID

Question 11

How many segments do heavy chains have?

Answer 11

3

Question 12

WHich chain goes under rearrangement first

Answer 12

Heavy

Question 13

What happens when the B cell bind with antigens and transduces a signal through BCR?

Answer 13

Starts as a naïve B cell

It is stimulated by antigens and interacts with T cells

It will go into lymph nodes (B cell areas)

Question 14

What are the three Possible Pathways once it has recognised an antigen:

Answer 14

Affinity Maturation - antibody response improves

Memory Cell - becomes stored for later exposure to the same infection

Plasma Cell - B cells which physically make the antibody

Question 15

Where do the acessory signal for b cells come from

Answer 15

Directly from microbial constituents

T helper cell

Question 16

How is antibody production by B cells achieved?

Answer 16

T cell dependent 
T helper cell 
Broader family  
Protein based antigens 
All Ig classes 

T cell independent
ONLY IgM
Recognise microbial constituents
Associated with polysaccharide

Question 17

Describe the process of making T Independent Antigens

Answer 17

Main thing it’s related to is polysaccharides

The polysaccharide has a repeating subunit

Because the molecule is long and repeating it binds to lots of BCR on the same cell and drive cross-linking.

One molecule will be recognised by lots of different receptors and pulled into the same space.

You also need a secondary signal

In T independent antigens, the secondary signal is coming from microbial constituents - PAMPs such as LPS

Question 18

Describe the process of making T Dependent Antigens

Answer 18

The antigen has to be taken up by TWO TYPES OF CELL - B cell + Dendritic Cell

BCR recognises the antigen and pulls it into the cell

Once it has been pulled into the cell, the antigen is chopped up and put on the MHC class II - this is what allows APCs to interact with T cells

The loaded MHC class II is presented to a T cell which recognises it through TCR

CRITICAL POINT: B cell and DC both have the same antigen on their MHC class II

The T cell population expands and moves to lymph nodes

In the lymph nodes they bind to the B cell which has the same MHC class II with antigen

THIS PROVIDES THE SECOND SIGNAL

The B cell becomes a plasma cell

Question 19

What happens after the T helper cell binds to the antigen?

Answer 19

T helper cells secrete lymphokines after recognition of the antigenic/self complex on the surface of the B cell

B cell enters the cell cycle and develops into a clone of cells with identical BCRs

Question 20

Cytokines influence Ig classes

Answer 20

There are a number of different types of T helper cells defined by the type of cytokines they produce

Different cytokines will switch the kind of constant region on the antibody

The variable region remains the same (specificity is the same)

The type of T cell that the B cell is exposed to is critical in how the antibodies respond

Question 21

Ig Class Switch

Answer 21

Once the B cells are in contact with the T cell - the T cell drives the class switching

You keep the variable region and you switch out different exons to give you a different constant region.

Different effect

Question 22

What is Somatic Hypermutation and Affinity Maturation

Answer 22

AID (Activation-Induced Deamination) causes point mutations in the VDJ region which causes small changes in the B cell

It is an evolutionary process

AID - takes the DNA and change the C in GC to an A so that in the next generation you get a T on the opposite strand - these small point mutations cause slight changes in antibody structure.

This is important in improving the antibody response.

Best binding antibody producing b-cell survives the rest die

Question 23

What is Immunological Memory

Answer 23

Immunological memory is also a consequence of clonal selection

Can confer lifelong immunity to infections

Basis for vaccines

Affinity - the ability of the antibody to bind to an antigen

Affinity improves over time - the antibodies you produce the second time are better than the ones you generate on first exposure

Question 24

When B cells go bad

Answer 24

Antibodies play a role in a number of autoimmune diseases e.g. Myasethenia gravis

IgE is involved in anaphylaxis

Some B cells can turn into cancers (lymphomas and myelomas) especially under the influence of viruses e.g. Epstein-Barr Virus