Lecture: Infection and Immunity
Date: Friday 9th February
Time: 1pm-2pm
Generation of antibody diversity, B lymphocyte clonal selection and B cell Activation
This lesson will cover:
- How we produce enough antibody diversity.
- How we generate the right number of specificities and pathways that deal with
antibodies correctly.
- Antibody rearrangements before the B cell leaves the bone marrow.
- How does the B cell get help from the helper T cell in antibody diversity.
History:
Dr Susumo Tonegawa – awarded prize for gene segment recombination in 1987.
He used restriction enzymes to analyse genes. This research found that we cannot have one
gene for an antibody, but there are different components involved to get more specificity. If
you lack rag1 and rag2 enzymes, you cannot make B cell or T cell receptors. Those born
without these genes need to be kept in a bubble due to lack of adaptive immunity. This
disease is called SCID.
How do we rearrange to produce a light chain segment and hemi chain segment?
V and J join to each other the intervening sequences are chopped away so the B cells are
committed to V and J regions transcribed Spliced polypeptide chain.
The heavy chain has a set of blocks in blue that represent different classes of antibodies. It is
the constant regions that decide the class of the antibody.
They have attempted giving rag proteins to children in retro vile, but the only way is through
bone marrow transplant.
How can we produce the right number of specificities for pathogens?
In mouse models there are 85 variable light chain segments and up to 4 J segments. If we
multiply these, we get 340 possible combinations for light chain region.
Heavy chain variable region:
There are 134 variable segments and 13 possible diversity regions and 4 potential J or joining
segments. If we multiply these 3 we produce 6968 possible variable regions.
When multiplying 6968 by 340 we have 2,370,000 possible antigen specificities. To increase
diversity up to 1000-fold further, variability in the joining of gene segments together occurs
as well as random somatic throughout the variable regions of both heavy and light chains.
1
Date: Friday 9th February
Time: 1pm-2pm
Generation of antibody diversity, B lymphocyte clonal selection and B cell Activation
This lesson will cover:
- How we produce enough antibody diversity.
- How we generate the right number of specificities and pathways that deal with
antibodies correctly.
- Antibody rearrangements before the B cell leaves the bone marrow.
- How does the B cell get help from the helper T cell in antibody diversity.
History:
Dr Susumo Tonegawa – awarded prize for gene segment recombination in 1987.
He used restriction enzymes to analyse genes. This research found that we cannot have one
gene for an antibody, but there are different components involved to get more specificity. If
you lack rag1 and rag2 enzymes, you cannot make B cell or T cell receptors. Those born
without these genes need to be kept in a bubble due to lack of adaptive immunity. This
disease is called SCID.
How do we rearrange to produce a light chain segment and hemi chain segment?
V and J join to each other the intervening sequences are chopped away so the B cells are
committed to V and J regions transcribed Spliced polypeptide chain.
The heavy chain has a set of blocks in blue that represent different classes of antibodies. It is
the constant regions that decide the class of the antibody.
They have attempted giving rag proteins to children in retro vile, but the only way is through
bone marrow transplant.
How can we produce the right number of specificities for pathogens?
In mouse models there are 85 variable light chain segments and up to 4 J segments. If we
multiply these, we get 340 possible combinations for light chain region.
Heavy chain variable region:
There are 134 variable segments and 13 possible diversity regions and 4 potential J or joining
segments. If we multiply these 3 we produce 6968 possible variable regions.
When multiplying 6968 by 340 we have 2,370,000 possible antigen specificities. To increase
diversity up to 1000-fold further, variability in the joining of gene segments together occurs
as well as random somatic throughout the variable regions of both heavy and light chains.
1
