5 - B lymphocytes Flashcards
KEY FACTS
- B cells make antibody
- B cells come from the bone marrow
- B cells are a critical component of the adaptive immune response.
- Encode the Antibody they will make on their surface (BCR)
- Antibody diversity comes from Ig gene rearrangement (VDJ)
- B cell response can be T dependent (protein) or T-Independent (Polysaccharide)
- B cells become plasma cells (antibody factories)
- Antibody quality improves over time (affinity maturation)
What is clonal selection?
Each lymphocyte (B and T) is specific for a particular antigen and the specificity of binding resides in the receptor for antigen (B cells: BCR = B cell antigen receptor; T cell: TCR = T cell antigen receptor). T cells use a similar process than B cells to generate diversity.
Note: the mechanism used to generate antigen-specific receptors on B and T cells seems to be unique in the entire body, no other genes use the rearrangement strategies.
What is the purpose of immunoglobulin gene rearrangement?
Ensures that when any foreign antigen enters the body there will be a few B lymphocytes with immunoglobulin (Ig) molecules on their surface able to bind that antigen.
What happens after an antigen has minded to the antibody on the B lymphocyte?
After binding the antigen, such a lymphocyte will divide to form a clone of identical cells with the capacity to produce antibody of this specificity.
Each B lymphocyte in the body has the capacity to make antibody of only one specificity. The antigen thus ‘selects’ a clone which has the capacity to produce antibody able to bind that antigen.
How many chromosomes are involved in coding for Ig chains?
Three chromosomes are involved in coding for Ig chains. One is responsible for kappa light chains, one for lambda light chains and one for all the heavy chains.
The principles of re-arrangement are the same for all three.
Where are the genes stored for the different regions?
The genes coding for the variable regions are stored together upstream of the genes for the constant region. In this way it is not necessary to repeat the constant region DNA for each different variable region.
What happens during rearrangement?
During re-arrangement, which will convert a progenitor B cell into a functional B cell, one of the V segments comes together with one of the J segments.
- Unwanted DNA is looped out by a special mechanism.
- A primary RNA transcript is produced consisting of VJ linked to the constant region(C).
- Unwanted RNA between J and C is spliced out to give mRNA for VJC. This can then be translated into the light chain.
How does this differ for heavy chains?
The process is similar for lambda light chains and the heavy chains, but for the heavy chains there is a series of D segments between the V and J segments and the mRNA thus represents VDJC.
How else is diversity achieved?
Diversity is further extended by…
- variation in the precise joining points of the V, D and J segments,
- somatic mutation of the rearranged genes
- the random pairing of H and L chains to make the Ig molecule.
The number of different antibody specificities that can be produced by these processes is enormous.
What is class switching?
The heavy chain constant genes are sited one after the other, starting with Cμ, following the variable region genes. Under the influence of T cells, a process of class switching can occur in which the already re-arranged VDJ can switch its attachment from Cμ to Cγ, Cα or Cε. This produces the different classes of antibody but does not affect antibody specificity.
What are the 3 outcomes to B cell activation?
- Production of antibody as plasma cells (Clears current infections)
- Differentiation into memory cells (Prepares for future infections)
- Enters somatic hypermutation and affinity maturation (improves quality of antibody)
What are the 4 steps of T dependent activation?
- The membrane bound BCR recognises antigen
- The receptor-bound antigen is internalised and degraded into peptides
- Peptides associate with “self” molecules (MHC class II) and is expressed at the cell surface
- This complex is recognised by matched CD4 T helper cell and the B cell activated
How does a memory response work?
- The immune system not only recognises and responds to antigen, it also can “remember” subsequent encounters with the same pathogen
- Memory responses are characterised by a faster and stronger immune response that serves to eliminate pathogens and prevent diseases. The response will often have a greater affinity.
- Memory can confer life-long immunity to many infections
