B cell biology

Question 1

What are the key features of B cells?

Answer 1

1. They are cells of the adaptive immune system.
2. Each B cell has a unique B cell receptor (BCR)
3. They recognise antigen in any biological form
4. Once they recognise an antigen they proliferate and differentiate into plasma cells
5. Each plasma cell produce trillions of antibodies
   (immunoglobulin = Ig) and are secreted into circulation and mucus membranes.

Question 2

List the steps of B cell development.

Answer 2

1. Pro-B cell is a committed B cell
2. Pre-B cell occurs when cells undergo gene rearrangement to make a pre-BCR (made up of two Ig M heavy chains and two surrogate light chains)
3. Immature B cell occurs when cells undergo gene rearrangement to replace surrogate light chains with either two Ig κ or two λ light chains. This makes a membrane bound IgM antigen receptor BCR)
4. Mature B cell occurs when a IgD receptor is coexpressed with the IgM receptor (IgM+
   IgD+ B cell) – this steps happens in the spleen

Question 3

Discuss B cell receptor arrangement.

Answer 3

1. A membrane bound IgM is also called the BCR.
2. It is composed of four polypeptide chains:
   - 2 heavy chains and 2 light chains
3. Assembled to form a ‘Y’ structure.
4. The heavy and light chains are attached via
   disulphide bonds
5. Each domain folds into a characteristic 3D shape
   called the ‘Ig domain’
6. The V region is the variable ‘antigen
   -binding site’ and the C region is the constant region

Question 4

Discuss gene rearrangement of BCR genes.

Answer 4

1. There are 9 different C regions which code for the constant region of the heavy chain. The expression of Cm is essential for the generation of the IgM BCR.
2. The H locus contains multiple VDJ segments which recombine randomly and code for the variable region of the heavy chain
3. Gene rearrangement of the light chain occurs on the Ig κ locus (chromosome 2) or Ig λ locus (chromosome 22)

Question 4

List the steps involved in B cell activation.

Answer 4

Question 5

Describe the structure and functional elements of antibodies.

Answer 5

1. Antibodies are secreted proteins which recognise
   ‘epitopes’ on the surface of pathogens using
   their antigen binding site within the variable
   regions.
2. Epitopes can be any biological molecule.
3. The constant region activates different effectors
   that eliminates these microbes and toxins.
4. The ‘type’ of constant region defines the isotype
   of an antibody

Question 6

Define isotype switching.

Answer 6

1. IgM is the first antibody secreted upon infection, but B cells can isotype switch into making IgG, IgA, IgE, IgD isoforms as required
2. During isotype switching the antigen binding site remains the same but the constant region of the heavy chain is replaced.
3. This process is induced by CD40-CD40L interaction and cytokines released by T helper cells.

Question 7

Define Affinity maturation.

Answer 7

1. The process by which the affinity of antibodies produced in response to an antigen increases with prolonged or repeated exposure.

Question 8

List the different classes of antibodies and what they do.

Answer 8