Immunoglobulin genes Flashcards
what is the difference in genes for a cell thats non-lymphoid and cell thats destined to become a B Cell?
non-lymphoid cells will have genes that produce Ig’s very far apart. This is germ line configuration
cells becoming B cells will have Ig genes close together due to somatic recombination
What are the DNA segments of light chain and DNA segments of Heavy chain. What segments form what parts of the antibody?
light chain
- variable –> V and J make the variable region
- joining —->
- constant –> makes constant region
heavy chain
- variable —> VDJ make variable
- diversity
- joining
- constant –> makes constant
true or false, lambda and kappa light chain gene segments are located on different chromosomes
true –> kappa is expressed more
what is the order of genes for the light chain?
Leader –> variable –> joining –> constant
what is the main difference between kappa and lambda light chains?
lambda light chain has 4 constant genes. For each one, there is one J gene located upstream of it.
–J1–C1—J2—C2 –> always selected together
for Kappa light chain there is only one C region and therefore the J regions randomly select to attach to it.
–J123456——C1—–
what is the organization of the heavy chain gene locus?
leader –> variable –> diversity —> joining –> constant
VDJC
t or f, the heavy chain is found on a different chromosome as the kappa and lambda chromosomes.
true
what is the first two constant genes on the heavy chain?
IgM comes first always!! IgD comes second most of the time.
Does the first gene rearrangement occur in the H or L chain?
always the H chain
how many gene rearrangements occur for heavy chain ?
two
what are the gene rearrangements for the heavy chain?
- DJ –> a Diversity segment RANDOMLY joins a particular joining segment. Everything in between is excised.
- Then a variable segment randomly joins the DJ segment. Again everything in between is excised.
what two enzymes are responsible for cleaving the DNA and causing recombination?
RAG-1 and RAG-2
Once the two rearrangements have occurred, what steps occur until the final heavy chain product is made (4)
- transcription of modified DNA
- RNA processing
- Poly A tail added to Constant side
- splicing of excess mRNA - translation occurs
- protein is processed and sent to cell surface
what occurs to the leader segment of the heavy chain?
its translated but cleaved off in protein processing
What are the 9 functional gene segments of the heavy chain constant region?
IgG -gamma 1-4 IgM IGA - alpha 1 and 2 IgD IgE
true or false, diversity gene segments are in lower numbers for heavy and light chains.
false.
there is no D segment in light chains
in heavy chains there are quite a few D genes.
After the heavy chain has been recombined, how does the light chain get recombined?
there is only one gene rearrangement in which V joins with J !!
V—J—C
VJ—-C
depending on Kappa or lambda for which J is combined with V
t or f, same processing occurs for light chain as it does for heavy.
true
transcription
mRNA processing –> splicing, polyA tail
translation
protein modification
What is the functional unit of the gene locus that allows for gene recombination (i.e. where do RAG-1 and 2 act)?
RSS –> recombination signal sequences.
explain how RSS’s work.
RSS segments flank each gene (variable, diversity if heavy, joining, and constant)
they are heptamer – (12/24)–nonamer
12 = a single turn RSS 24 = a 2 turn RSS # = nucleotides only single turns can pair with 2 turns (NOT 1:1 or 2:2)
RAG enzymes recognize these sequences and cause excisions
what does a turn refer to in RSS?
the number of nucleotide in a turn of helix in DNA
t or f, the heptamer and nonamer sequences of RSS are conserved but the 12/24 isnt.
true.
what is the purpose of RSS’s?
prevent improper gene rearrangement.
explain the RSS organization of a heavy chain? Why does this prevent improper gene rearrangement?
Vh > (24) ——– ———< (24)J
since variable and joining chains are both two turn RSS’s they cannot recombine. This forces D to combine J first (DJ) and after V then combines with DJ to get VDJ which then gets transcribed.
true or false, VDJ and VJ rearrangements (i.e. heavy chain and light chain) occur continuously over a B cells life.
false, they occur once!! After this, the B cell only secretes that antibody that was recombined for. (for a given epitope)
