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37 Cards in this Set

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  • Back
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?
-Heavy chain
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
4. P-addition
5. N-addition
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?
What happens?
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.