Generation Of Lymphocyte Ag Receptors

Front 1

Somatic Diversification Theory

Back 1

Ig repertoire is generated from limited number of gene segments.

Front 2

Where does somatic recombination of DNA occur?

Back 2

B cells

Front 3

How was somatic recombination discovered?

Back 3

Southern Blot comparing non-lymphoid and B cells

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Front 4

Light Chain

Back 4

has one V(L) and one J(L) segment.

Front 5

Heavy Chain

Back 5

Has one V(H), one D(H), and one J(H)

Front 6

Enzymes involved in recombination

Back 6

Enzyme complex = VDJ recombinase

RAG1 = recombination activation genes
RAG2 = code for the lymphocyte-specific components.

Front 7

Knockout Mouse Technique

Back 7

1. A mutant version of the preselected target gene is constructed in the lab.
2. Knockout is achieved by swapping the functional copy of the gene for the mutated version in mouse ES cells.
3. Mice then are derived from these ES cells carrying the same mutation in every cell.
4. An additional round of breeding is required to produce mice that are homozygous for the mutation.

Front 8

AB diversity is generated by 4 main processes

Back 8

Before Ag exposure (is random)
1. Combinatorial Diversity (VDJ choices) = multiple inherited gene segments are used in different combinations.
2. Junctional diversity (imprecise joining) = Variable addition and subtraction of n.t. at junctions between gene segments contributes to diversity in the 3rd hypervariable region.
3. H and L combination

After AG exposure
4. Somatic hypermutation = Accounts for further diversity

Front 9

TCR Gene Rearrangement

Back 9

1. Combinatorial Diversity
2. Junctional Diversity
3. H and L Combination

NOTE: unlike Ab gene rearrangement, there is no somatic hypermutation. Each individual controls their TCRs.

Front 10

Structural Variation in Ig Constant Regions

Back 10

The pathogen drives the "switch" of cassettes that are the constant regions.

Front 11

Why is it beneficial to have multiple copies of V, D, and J gene segments?

Back 11

creates diversity

Front 12

Why is it not a good idea to have T cells that can somatically hypermutate their TCRs?

Back 12

This is the main way we prevent auto-immune issues.

Front 13

Which antibodies are co-expressed?

Back 13

IgM and IgD can be expressed simultaneously on the cell surface.

Front 14

Ab functional specialization

Back 14

Controlled by the constant regions.

- C' activation
- Allows binding to different Fc receptors.