Glossary of Immunoglobulin Genes
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- How many multigene families are there for Heavy Chains and Light Chains?
- One for each type of chain.
-one heavy chain multigene family
-one light chain multigene family
Each family contains many gene segments.
- There are many gene segments on the Kappa-chain (light) multigene family;
-How many V segments?
-How many J segments?
-How many C segments?
Only one of each segment type contributes to the light chain protein.
- What are the three types of multigene families?
- What gene segment types contribute to variable regions on antibodies?
- VJ and VDJ
- What gene segments contribute to non-variable (Fc) regions of antibodies?
- describe the gene segment rearrangement process in general, and where does it occur?
- random gene rearrangement that occurs in the primary lymphoid organs = thymus and bone marrow.
- What are the 2 main components of the mechanism that allows/directs gene rearrangement?
- 1. RSS - Recombinational Signal Sequences
2. Enzymatic gene segment joining
- What are RSSs?
How many types are there?
- Recombinational Signal Sequences.
They show where recombination (making joints) should occur.
2 types: One-turn RSS and two-turn RSS;
- What is the significance of the two different types of RSSs?
- One-turns recognize 2-turns. They recognize each other;
The D segments only have 1-turn on either side of the segment, The V and J segments only have 2-turn.
Therefore, V can only join D, and VD can only join J. (no VJD)
- What enzymes participate in enzymatic joining of gene segments?
- Rag-1 and Rag-2
Terminl deoxynucleotidyl transferase (TDT)
- What are RAG 1/2?
What do they do?
- Recombination activating genes.
-Bring together RSS's
-Cut DNA to form HAIRPIN
- What does Endonuclease do?
- Cuts the hairpin formed by RAG1/2.
To form a place to do P- and N-additions.
- What is P-addition?
- Addition of nucleotides to the cleaved hairpin (by endonuclease). Forms a
- What is N-addition?
What does it?
- Addition of Nucleotides to cut hairpin.
Terminal deoxynucleotidyl transferase
- What repairs the dna after Gene segment joining and hairpin/addition?
- DSBR - doubl. strand break repair enzymes; repair/join coding sequences.
- 2 results of random gene rearrangement/joining:
- -formation of coding joint
-formation of signal joint.
- What is the "coding joint" a code for?
- the variable regions (VJ and VDJ) of the immunoglobulin DNA.
- If you don't have Rag enzymes or DSBR, what is the result?
- SCID - severe combinatorial immune deficiency
- What is Evidence for gene rearrangement?
- presence of circular dna in the thymus
- what is "junctional flexibility"?
- imprecise joining of the coding sequence.
Meaning, codons are 3-aa sequences; if a V and J segment join and make a STOP codon, it is NONPRODUCTIVE.
- 2 products of junctional flexibility:
what is the consequence?
- In-phase or Out-of-phase joining.
In-phase can be translated.
Out of phase contains a premature stop codon and will not be translated into protein.
- What is unique about Rag 1/2 and TdT expression?
- only occurs in lymphoid cell lines; that's the only place where this REARRANGEMENT occurs; not in other chromatic DNA.
- Why do T and B cell genes rearrange?
- to create a diverse reportoire of cells that can recognize all different Ags.
- What do animals with defective gene rearrangement lack?
- MATURE B/T cells; leads to SCID, the lack of ANY specific immune response;
- What mechanism produces either Membranous or Secretory Ig?
- Differential RNA processing.
- Which cells have Membranous Ab?
Which cells have Secretory Ab?
- Membranous: Native/memory B cells
Secretory: Plasma cells - the effectors
- What is Allelic exclusion?
When does it happen?
What is the significance?
- the inhibition of one copy of the Ig genes (from one parent) so that only one set is expressed. Occurs once one set is properly rearranged.
Significance: if you had two sets expressed, you would have two antibody clones for the same antigen.
- What is Somatic Hypermutation?
WHERE does it happen?
When does it happen?
- -Random gene mutations on the VJ or VDJ gene segments.
-In activated B cells, in the germinal center.
-After activation by Antigen.
-to generate different affinities in the antibodies, to select the best population.
- 7 things that generate ANTIBODY diversity:
- 1. Fact that there are multiple gene segments in each multigene family.
2. Random combinations of those segments.
3. Junctional flexibility
6. Somatic Hypermutation
7. Combinatorial association of LC and HC
- What follows somatic hypermutation?
- Affinity maturation
to select the B cells with better affinity that was generated by the random mutations of somatic hypermutation.
- What maturational level are the B cells that undergo
-Variable region rearrangement
-Constant region rearrangement
- Variable: immature, in the primary lymphoid organs.
Constant: Mature, in the peripheral lymphoid tissues, after Ag activation. Then they differentiate into effector/memory cells.
- What is the mechanism of class switching? When/where?
- DNA looping; after Ag stimulation, in the peripheral lymphoid tissues.
DNA loops and VDJ joins with one of the Constant heavy segments.
- What does class switching explain?
- How one specific mother antibody clone can have different effects (different Fc regions).
- What Switch Factor tells the Bcell which class to switch to?
- What does Differential RNA processing allow?
- Expression of both IgM and IgD on one naive B cell - the two differ in which membrane is bound, but b
- What is Differential RNA processing?
- Cleavage of the RNA transcript (ripe and ready for expression) before or after segments that encode secretory or membrane-bound genes for the C region.
- Why can IgM and IgD be expressed in one naive B-cell simultaneously?
- There's no switch site between their C gene segments; the RNA transcipt is not cleaved during RNA processing, so they both get transcribed and translated.
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