5 B-Lymphocytes

Question 1

Q: Explain the origin and maturation of B lymphocytes.

Answer 1

A: 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

Question 2

Q: What is the BCR? How does it function?

Answer 2

A: B Cell Receptor- where specificity resides

The BCR is a transmembrane protein complex consisting of a membrane-anchored antibody and di-sulphite linked heterodimers Igalpha and Igbeta- aids extracellular signal detection

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

The BCR have a unique binding site which binds to the epitope.

Question 3

Q: Describe clonal selection of the B cell. What does it lead to?

Answer 3

A: Each lymphocyte has a single, unique receptor

Interaction between BCR and antigen leads to activation

Activation causes proliferation of the relevant B cell

Question 4

Q: Define epitope.

Answer 4

A: region of an antigen that the antibody binds to

Question 5

Q: Define antigen.

Answer 5

A: proteins or molecules that induce an adaptive immune response

Question 6

Q: Where does the main difference between B and T lymphocytes reside?

Answer 6

A: TYPE OF EPITOPE they recognise:

T cells - identify the sequence
B cells - identify the structure (tertiary)

Question 7

Q: What are the two types of adaptive immune response?

Answer 7

A: Humoral: B cells - antibodies

Cell-Mediated: T cells - cytokines, killing

Question 8

Q: Is the repertoire of BCR preexisiting or does it need to be stimulated?

Answer 8

A: The repertoire of BCR you have exists before you are exposed to any antigens

Question 9

Q: What are Igalpha and Igbeta? Why are they useful?

Answer 9

A: heterodimers- have an immunoglobulin like fold

The cytoplasmic tails of the mIg (membrane-bound Ig) is too short to signal

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

Question 10

Q: What generates antigen receptor diversity?

Answer 10

A: recombination- IMMUNOGLOBULIN GENE REARRANGEMENT

Question 11

Q: Describe immunoglobin gene rearrangement in the BCR.

Answer 11

A: 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

Question 12

Q: How is a standard membrane protein expressed?

Answer 12

A: Start off with genome DNA - exons and introns
Transcription - RNA produced
Splicing - RNA spliced
Translation - polypeptide produced

Question 13

Q: How is the immunoglobin light chain expressed?

Answer 13

A: There are 70 variable units that people have - 40 in kappa and 30 in lambda- 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 V and J regions (this is random)

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

• > mRNA -> Different splicing patterns give rise to further variation
• > protein -> polypeptide

Question 14

Q: Describe heavy chain gene rearrangement?

Answer 14

A: You start off with germline DNA

The different regions shuffle and rearrange via recombination

A few V, D and J regions are passed down

The constant region is what determines the type of antibody e.g. alpha constant region gene gives rise to IgA

• > mRNA -> Different splicing patterns give rise to further variation
• > protein -> polypeptide

Question 15

Q: Does the heavy or light chain undergo gene rearrangement first?

Answer 15

A: Heavy Chain undergoes VDJ rearrangement FIRST

Light chain then undergoes VJ rearrangement

Question 16

Q: What happens when B cells bind with antigens and transduces a signal through BCR? What else does this process require?

Answer 16

A: Starts as a naïve B cell

It is stimulated by antigens and interacts with T cells

Three Possible Pathways once it has recognised an antigen:
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

Can’t be activated by antigen along: Naïve B cells require an accessory signal - this is costimulation

For B cells, accessory signals come from:
Directly from microbial constituents
T helper cell

Question 17

Q: How is antibody production by B cells achieved?

Answer 17

A: 2 pathways for 2 types of antigen that it can detect= T cell (thymus) dependent & T cell (thymus) independent

Question 18

Q: Explain the activation of B cells via T independent antigens.

Answer 18

A: Main thing it’s related to is polysaccharides

Because the polysaccharide molecule is long and has repeating units 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 = clustering of Ig provides a signal strong enough for B cell activation

You also need a secondary signal

In T independent antigens, the secondary signal is coming from microbial constituents - PAMPs such as LPS (no need for T helper cells etc)

-> leads to upregulation and release of IgM- no class switching

Question 19

Q: Explain the activation of B cells via T dependent antigens.

Answer 19

A: activation by protein based antigen

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 -> 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- can produce all Ig classes

Question 20

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

Answer 20

A: 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 21

Q: How do cytokines affect Ig classes?

Answer 21

A: There are a number of different types of T helper cells (Th1 and Th2)- These two types of T helper cell are defined by the type of cytokines they produce

The type of cytokine produced have an effect on the type of antibody produced - Different cytokines will switch the kind of constant region on the antibody (The variable region remains the same (specificity is the same))

Question 22

Q: Explain Ig class switch?

Answer 22

A: Once the B cells are in contact with the T cell - the T cell drives the class switching - switch out different exons

B cell changes its DNA so that it produces a different constant region while keeping the variable region

Question 23

Q: Why is the immune response stronger and faster the second time round? (improves)

Answer 23

A: due to somatic hypermutation and affinity maturation

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

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

Question 24

Q: Define affinity maturation.

Answer 24

A: process by which T cell-activated B cells produce antibodies with increased affinity for antigen

Question 25

Q: Define somatic hypermutation.

Answer 25

A: mechanism by which the immune system adapts to the new foreign elements that confront it (e.g. microbes), as seen during class switching.

Question 26

Q: What is an immunological memory?

Answer 26

A: Immunological memory is also a consequence of clonal selection

Can confer lifelong immunity to infections

Basis for vaccines