Term
| Length and location of V, D and J gene segments |
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Definition
5' end: ~300 bp V region
Downstream of the this are 30-50 bp J segments
In H chain:
further toward the 3' end are the D (diversity) segments |
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Term
| What do the D and J genes code for? |
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Definition
| C terminal of the V regions, including the third CDR of antibody molecules |
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Term
What codes for the variable region in light chains?
What codes for constant region? |
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Definition
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Term
What codes for the variable region in heavy chains?
What codes for the constant region in heavy chains? |
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Definition
- Variable: V, J, D
- Constant: multiple C exons |
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Term
Order of re-arrangements of for heavy chain
What happens to intervening DNA?
Which step is the critical control point? |
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Definition
1) DJ: deletion of intervening DNA
2) VDJ: all D segments between are deleted (critical control step)
3) VDJ + C: C remains separate via an intron so DNA is not deleted between these |
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Term
| Light chain order of rearrangements |
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Definition
1) VJ: intervening DNA is deleted
2) VJ + C: C is still separated by an intron which will be spliced |
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Term
What is the youngest cell type to synthesize a detectable Ig gene product?
Where is it found? |
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Definition
Pre-B
- bone marrow or fetal liver |
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Term
| What rearrangements have pro-B cells undergone? |
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Definition
| - Heavy chain DJ, no light chain |
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Term
| What is the pre-B cell surface receptor comprised of? |
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Definition
| μ-chain, surrogate light chain, Igα, Igβ |
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Term
What is RSS?
Where are RSS found on the heavy and light chains, how long are they?
Which enzyme mediates this? |
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Definition
Recomination signal sequence
-Light chain: 3' end of V, 5' end of J
in λ light chain: V= 23, J=12
in Κ ligh chain: V=12, J=23
- Heavy chain: 3' end of V (23), 5' end of D (12)
3' end of D (12), 5' end of J (23)
RAG 1 and Rag 2
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Term
| Mechanisms for antibody diversity |
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Definition
1) combinatorial joining: the cominatorial associations of different V,D and J gene segments lead to a large potential for generating different antibody specificities.
2) Imprecise end joining: light and heavy chains can recombine at any of several nucleotides in the germline
3) N-region addition: only heavy chain, nucleotides not in the germline can be added to the junctions of rearranged VDJ genes during rearrangment. |
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Term
What enzyme is responsible for heavy chain N-region addition?
Why doesn't it work on light chain? |
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Definition
TdT - adds nucleotides w/o template
- TdT expression is shut off by the time light chain rearrangement occurs |
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Term
How many heavy chain V J and D segment possibilities are there?
Total possibilities? |
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Definition
H V gene: 40
H J gene: 6
H D gene: 25
~6000 |
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Term
| What cell type is a chornic acute lymphoblastic leukemia (ALL) comprised of? |
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Definition
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Term
| What cell type is a Burkitt's lymphoma comprised of? |
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Definition
| - Mature memory B cell (germinal center) |
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Term
How many light chain combinations are there?
Total possibilities for each? |
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Definition
Kappa: V = 40, J = 5
- 200 total
Lambda: V = 30, J = 4
- 120 total |
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Term
What is the puprose of receptor editing?
Which chain can undergo receptor editing? |
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Definition
- fix self reactive B-cells or non functional B cells
- only takes place in light chain; it is a new rearrangement of V and J genes. This cannot happen in heavy chain without deleting D. |
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Term
What is sommatic hypermutation? What part of the gene does it take place in?
What is the result? |
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Definition
- changes in antigen binding specificity as a result of somatic mutations in V genes
- results in additional diversity |
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Term
| When does somatic hypermutation occur? |
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Definition
- Pre B and early B cells utilized unmutated germline V genes
- primary antibody response utlizes mostly unmutaed V genes
* secondary response utlizes genes that have increased affinity via somatic hypermutaiton |
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Term
| What cell type is a Hodgkins lymphoma tumor comprised of? |
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Definition
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Term
| What cell type is a multiple myloma tumor comprised of? |
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Definition
| - plasma cell (various isotypes) |
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Term
| Differnec between alpha and beta cahin loci of T-cells |
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Definition
- alpha: 70-80 V gene options, 61 J gene options
- Beta : 52 V gene options, several D gene options and 7 J gene options
*beta has D, alpha does not! |
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Term
Which chain options for T-cell receptors do alpha and gamma have for their variable regions?
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Definition
| - their variable regions: J and V |
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Term
What is different about N-segment addition in T-cell receptors?
What feature does limit their diversity, however? |
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Definition
both chains (alpha and beta) can undergo N-segment addtion
- T cells do not undergo somatic hypermutation |
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