Term
| All B and T lymphocytes receptor genes are put together from |
|
Definition
| lots of rearranged gene segments..some even on different chromosomes. |
|
|
Term
| How many sets of light chain genes does each B cell have for rearrangement? |
|
Definition
|
|
Term
| How many sets of heavy chain genes does each B cell have for rearrangement? |
|
Definition
|
|
Term
| During development, which set of immunoglobulin chains does a B cell arrange first? |
|
Definition
|
|
Term
| What gene segments must be recombined to code for the variable region of a light chain protein? |
|
Definition
|
|
Term
| What gene segments must be recombined to code for the variable region of a heavy chain protein? |
|
Definition
|
|
Term
| Where is the site of cleavage |
|
Definition
The Recombination Singal Sequence
RSS |
|
|
Term
| What is the RSS (Recombination Signal Sequence ) made of? |
|
Definition
| hePtamer nonamer reminder: HePTamer and NoNamer |
|
|
Term
| What is the hetamer and nonamer seperated by .. and what never changes? |
|
Definition
| seperated by spaces 12 or 23 bp the bases can change but those numbers remain the same. |
|
|
Term
Theories: Germ line
Somatic
Dreyer and Bennet |
|
Definition
germ line that mom and pop just gave lots of Ig genes Somatic.. that there were mutations
Dreyer and Bennet said the were on different chromosome. |
|
|
Term
| The antibody light-chain gene encodes __families of DNA segments. |
|
Definition
|
|
Term
During B-cell development, one V seg-
ment and one J segment (which encode contiguous parts of the _____) join together with the C (constant) region to form the gene for the antibody light chain. This gene rearrange-
ment occurs in the DNA, prior to gene transcription into mRNA. |
|
Definition
light-chain variable region
(one V segment, one J segment, |
|
|
Term
| each gene segment V, D and J has as adjacent ___ |
|
Definition
| RSS Recombination Signal Sequence at the 3' end of each V, both ends of each D, and the 5'end of each J |
|
|
Term
| What proteins are the RSS recognized by |
|
Definition
RSS is recognized by
2 Recombination Activating Genes
RAG-1 RAG-2 |
|
|
Term
| What does RAG 1 and RAG-2 proteins do? |
|
Definition
| Cut both strands of DNA at the RSS |
|
|
Term
| After the CUT by RAG 1 and RAG 2...forming double stranded breaks how is it repaired? |
|
Definition
| by nonhomologous end-joining.... the cuts ends are ligated or stitched together... |
|
|
Term
| What was cut out by RAG 1,2? |
|
Definition
| All the stuff between the DNA present between the 2 gene sections.. DJ joining happens first (in Heavy ones) |
|
|
Term
|
Definition
| enhancers are located between the last (3' end) J segments and the C mu gene segement they draw the chromosom into loops bringing gene segments to be transcribed into premRNA close together and move the cluster to the center of the nucleus ... SCID can be from V(D)J joining defects. |
|
|
Term
| What are some things that could cause SCID Severe combined immunodificiency? |
|
Definition
| defects in V(D)J joining/ mutated RAG-1 or RAG-2/ mutations in gene for nonhomologous end joining..like without a coding joing... |
|
|
Term
The V region diversity almost infinite
because |
|
Definition
1.just putting 51Vh, 27 Dh and 6 Jh gene segement randomly together.
2. the exact points of splicing between Vh and Dh and Dh and Jh can vary 3. extra nucleotices called N regions can be inserted at these joints... that is a lot of diversity to CDR3 CDR3? |
|
|
Term
|
Definition
| Once the H chain gene is assembled, trnscred and translated..it can pair with a ligh chain (I think) |
|
|
Term
| what gene is the light chain kappa gene segment on? |
|
Definition
|
|
Term
| what gene is the light chain lambda gene segment on? |
|
Definition
|
|
Term
| What's the problem with all this recombinging and randome adding of nucleotides? |
|
Definition
| High risk of of introducing a frameshift so the codons for the rest of the V region encode nonsense. so lot of B cells are a waste |
|
|
Term
| What keeps from wasting so many B cells? |
|
Definition
| If it fails on one of its chromosomes it can turn to the gene segemtn on its homolog and try again...if it fails both times...to make a good kappy L chain it can still try at aming a functional lambdo L chain... |
|
|
Term
| The new B cell has never seen an antigen. Once it matures and see an antigen it can what? |
|
Definition
| it may begin mitosis, growing into a clone of cells with the same BCR...and secreting those antibodies.../Point mutation can happen where some might see the epitope even better or maybe worse.. the better ones are favored to subclone and maybe enen replace the original...AFFINITY MATURATION=antibodies of ever incrasing affinity for the antigen |
|
|
Term
| After B cells grown into a close int response to antigen, the can rearrange DNA once again... how? |
|
Definition
| The heavy chain can cut the gen on the 3' side of the assenbled V region segemtns and more the assemby to the 5' side of another Ch gene segemtn... the cell can begin to make a different class of antibody IgG, IgA..etc but the antigen spedificity of the antibody stasy the same because of the N terminal of the H chain staying the same (as does the entire, whole L chain). |
|
|
Term
| What does changing class help with? |
|
Definition
| Class swithc recombination enables he body to make antibodies with different effector functions different means of dealing with the same antigen |
|
|
Term
| The ability of a B cell to switch Constant heavy segments depends on what? |
|
Definition
| Its receiving elop from helper T cells. |
|
|
Term
| A single B cell makes only one kind of ____________ |
|
Definition
| antibody specificity (One Vh and one VL allelic exclusion occurs.... plasma makes only one kind of antibody ... B cells break the rule with heavy cain isotypes... for the cell surface IgM IgD |
|
|
Term
| Ig genes undergo a process of ___ |
|
Definition
| somatic DNA recombination |
|
|
Term
Each of the 3 gene families, the kappa light chain family, the lambda light chain family
and the heavy chain family can be divided into __________________ |
|
Definition
| V-region genes and C-region genes. |
|
|
Term
| The κ, λ and H chains are located on separate _________. |
|
Definition
|
|
Term
| Vand C regions of the proteins, separated by stretches of _____________ |
|
Definition
|
|
Term
| At the 5' end of each Ig locus are the _____, each about 300 base-pairs (bp) long,separated from one another by non-coding DNA of varying lengths |
|
Definition
|
|
Term
| Downstream of the V genes are additional coding sequences, 30 to 50 bp long, which make up the _____ and, in the H chain locus only, ___________ |
|
Definition
joining(J) segments
the diversity (D) segments |
|
|
Term
The J and D
gene segments code for the carboxy terminal ends of the ____, including the third
hypervariable (complementarily-determining) regions of antibody molecules |
|
Definition
|
|
Term
| In an Ig light chain protein (κ or λ), the variable region is encoded by the ____________ |
|
Definition
|
|
Term
| the constant region is encoded by the by a ______. |
|
Definition
|
|
Term
All cells except B-lineage, including plasma cells contain Ig genes in
the germline configuration. ______only in B-lineage cells.
Rearrangements of Ig genes are the essential first steps in the production of antibodies. |
|
Definition
| The Ig genes are expressed |
|
|
Term
Heavy chain - is a rearranged __ ,
This VDJ recombination
occurs only in cells committed to become B lymphocytes and is a critical control point in Ig expression because only the rearranged V gene is subsequently
transcribed. The C region genes remain separated from this VDJ complex by an
intron. |
|
Definition
|
|
Term
After the heavy chain, the next somatic DNA recombination involves a light chain locus. One V segment is joined to one J segment, forming a VJ complex, whichremains separated from the C region by an intron, and this gives rise to the primary RNA transcript. Splicing of the intron from the primary transcript joins
the C gene to the VJ complex, forming an mRNA that is translated to produce the κ protein. The light chain assembles with the previously synthesized μ to form
the complete membrane IgM molecule, which is expressed on ____,
and the cell is now the immature B lymphocyte |
|
Definition
|
|
Term
ProB Cells: These cells are precursors of PreB cells. They have IgH DJ gene rearrangements
and no _____. |
|
Definition
| light chain gene rearrangements |
|
|
Term
All B lymphocytes arise in the bone marrow from a stem cell that does not
produce __. The earliest cell type that synthesizes a detectable Ig gene product contains cytoplasmic mu-heavy chains composed of variable (V) and constant (C) regions. This
cell is called the pre-B lymphocyte and is found only in hematopoietic tissues, such as the bone marrow and fetal liver. The pre-B receptor is comprised of surrogate light
chain, mu-chain, Ig alpha and Ig beta |
|
Definition
|
|
Term
| kappa and Lambda light chain gene families contain ______gene segments |
|
Definition
|
|
Term
| heavy chain gene families contain ___________gene segments |
|
Definition
|
|
Term
| For all _____ families the C regions code for the constant regions |
|
Definition
|
|
Term
| ______ has 35 to 48 functional genes, 8 ORFs and 30 pseudogenes |
|
Definition
| V Kappa (ORF = open reading frame containing no stop codons) |
|
|
Term
| ___ has 5 functional; multiple alleles |
|
Definition
| J kappa (alleles = Alleles are corresponding pairs of genes located at specific positions in the chromosomes |
|
|
Term
| ____ has 5 functions: 2 ORFs: 79 pseudogenes |
|
Definition
|
|
Term
| ____ has 5 functional; 2 ORFS |
|
Definition
|
|
Term
| ____ has 38-44 functional; 4 ORGs: 79 pseudogenes |
|
Definition
|
|
Term
| ___ has 23 function: 4 ORFs |
|
Definition
|
|
Term
| ____ has 6 functional, 3 pseodogenes: several different alleles |
|
Definition
| J heavy (a pseudogene is one that has a stop codon and/or a frame shift mutation |
|
|
Term
At the germ-line level,
a functional lambda-variable region contains a 5’___and a 3’ ____
separated by _____.. |
|
Definition
V segment
J segment
a noncoding DNA sequence |
|
|
Term
| Jl4 is a pseudogene meaning it is______. |
|
Definition
| (defective gene), incapable of encoding a protein |
|
|
Term
| The V lambda and three function Jl gene segments are used to encode the variable region of ______ |
|
Definition
|
|
Term
The three functional C lambda genes are used to encode the ___of one of the three lambda chain
subtypes lambda 1, lambda 2, lambda 3. |
|
Definition
|
|
Term
DNA rearrangement can join the V lambda 1 gene segment with any of the ___, or the V lambda 2 gene
segment with the ____ gene segment. |
|
Definition
|
|
Term
Rearranged kappa and lambda genes
contain the following located 5’ to 3’: |
|
Definition
a short leader (L) exon
an intron
a joined VJ gene segment
a second intron
a constant region |
|
|
Term
A ___ ____is located upstream of
the L sequence. |
|
Definition
|
|
Term
| A primary mRNA is generated after _________ |
|
Definition
the rearranged light chain sequence is
transcribed from the L exon through the
stop codon of the C segment. |
|
|
Term
| ____ of the primary mRNA are removed by splicing. |
|
Definition
|
|
Term
| ___ mRNA exits from the nucleus and is ___ |
|
Definition
|
|
Term
As the mature mRNA leader sequence is translated it is directed to the lumen of the____. In the __ the ___is cleaved off and the finished product will be assembled with two heavy chains and an additional
light chains. |
|
Definition
ER endoplasmic reticulum
leader sequence |
|
|
Term
| The V, D, J segments combine to form the coding sequence for the _____region. |
|
Definition
|
|
Term
| At the end of the processes of gene rearrangement, each B cell contains _____ |
|
Definition
a single functional
variable-region DNA sequence for its heavy chain and another for its light chain. |
|
|
Term
As a result of the process, a mature, immunocompetent B cell is produced, which is committed
to producing antibody with a _____binding site coded for by the ____. |
|
Definition
specific antigen
rearranged V genes |
|
|
Term
Through the process of ___, a B cell that has undergone variable gene segment
rearrangement can express its rearranged variable region with different constant region
segments to produce different isotypes of the antibody each having the same antigen
specificity. |
|
Definition
|
|
Term
| Describe heavy chain variable rearrangement |
|
Definition
Two separate variable region
rearrangements occur:
D gene segment joins to a J
gene segment.
The DJ segment then joins a V
segment to generate a VDJ unit
that codes for the variable
region. |
|
|
Term
| In heavy chain rearrangement,5’ to 3’, this rearrangement produces: |
|
Definition
L exon, Intron, VDJ unit,Intron, and a
series of C gene segments. A primary mRNA sequence is generated starting from a promoter sequence located upstream of the L exon and ending after the Cd region. |
|
|
Term
The mRNA is alternatively spliced to
produce mRNA for _____ |
|
Definition
|
|
Term
| From immature B cells, mature mRNA encoding __ is made and translated to produce ___ protein. |
|
Definition
|
|
Term
In mature B cells mature mRNAs encoding ___ and ___are made and translated to produce both __ and __
proteins containing identical V region sequences. |
|
Definition
|
|
Term
| ____ flank each germ-line V, D, and J gene segment |
|
Definition
| Recombination signal sequences (RSS ) |
|
|
Term
| One RSS is located ________ |
|
Definition
| 3’ to each V gene segment and 5’ to each J gene segment, and on both sides of each D gene segment |
|
|
Term
| The sequences function as ____ leading to VDJ rearrangement. |
|
Definition
signals for
the recombination process |
|
|
Term
| The RSS consists of three elements: |
|
Definition
• An absolutely conserved, 7bp heptamer consensus sequence
• A less conserved spacer region (12-23 bp)
• A second conserved 9 bp nonamer consensus sequence |
|
|
Term
| One-turn RSS and two-turn RSS have characteristic locations with in the light and heavy chain..During rearrangement, gene segments adjacent to the one-turn RSS |
|
Definition
can join only with segments adjacent to the two turn RSS.
germ line DNA. 12 / 23 |
|
|
Term
| What are those characteristic 12/ 23 bp s in? |
|
Definition
|
|
Term
| Where are the 12 / 23 RSS located? |
|
Definition
| In the picture they are the pointed ends...located on the 3'end of V (23) both sides of D (12/12 and the 5' end of J (23) in the heavy chain...and in the light chain kappa starts with 12 //the lambda starts with 23 |
|
|
Term
| Where are the 12 / 23 RSS located? |
|
Definition
| between the heptamer and the nonamer that the RSS is made up of. |
|
|
Term
This joining rule ensures that for light chain genes, a V segment joins only to a J segment and not to
another V segment. |
|
Definition
| During rearrangement, gene segments adjacent to the one-turn RSS can join only with segmentsadjacent to the two turn RSS. |
|
|
Term
This joining rule ensures that for light chain genes, a V segment joins only to a J segment and not to
another V segment.
The rule also ensures that for heavy chain genes, V, D, and J segments join in proper order and that
segments of the same type do no join each other. |
|
Definition
| that only the one turn can join a two turn... 12/23 rule |
|
|
Term
| Recombination between ___ gene segments is required to generate a complete light chain gene. |
|
Definition
|
|
Term
| Recombination between ___ gene segments is required to generate a complete heavy chain gene. |
|
Definition
|
|
Term
Only ___ ___ ___ are uniquely expressed in
lymphocytes. |
|
Definition
|
|
Term
_____ are recombinases that catalyze the recombination events that occur during immunoglobulin heavy and light chain gene rearrangement. Also
function in T cell receptor gene rearrangment. |
|
Definition
|
|
Term
The expression of RAG 1 and 2 is developmentally
regulated in ____. |
|
Definition
|
|
Term
| The RAG 1 and RAG 2 complex binds ___ and catalyzes recombination. |
|
Definition
|
|
Term
| Name the proteins involved in F (D) J recombination |
|
Definition
RAG 1 and RAG 2
Tdt HMG 1 / 2 proteins
Ku70 and Ju80 heterodimers
DNA PKcs Artemis XRCC4
DNA ligans IV Cernunnos |
|
|
Term
| in recombination what is RAG 1 and RAG 2? |
|
Definition
| Lymphoid specific complex of 2 proteins that catalyze DNA strand breakage and rejoin to form signal and coding joints. |
|
|
Term
|
Definition
| Lymphoid-specific protein that adds N region nucleotides to the joints between gene segments in the Ig heavy chin and at all joints between TCR gene segments. |
|
|
Term
| What does HMG / 2 proteins do? |
|
Definition
| Stabilize binding of RAG 1 / 2 to recombination Signal Sequences (RSSs), particularly to the 23-bp RSS: stabilize bend introduced into the 23-bp spacer DNA by the RAG 1 / 2 proteins. |
|
|
Term
| Ku70 and Ku80 heterodimers |
|
Definition
| Binds DNA coding and signal ends and holds them in protein-DNA complex |
|
|
Term
|
Definition
| In complex with KU proteins, recruits and phosphorylates Artemis. |
|
|
Term
|
Definition
| Opens the coding end hairpins |
|
|
Term
|
Definition
| Stabilizes and activates DNA ligase IV |
|
|
Term
|
Definition
| In complex with XRCC4 and Cernunnos ligates DNA ends |
|
|
Term
|
Definition
| With XRCC4, activates DNA ligase IV |
|
|
Term
|
Definition
| RAG 1 2 and HMG proteins bind to the RSS and catalyze synapse formaton between a V and J segment. |
|
|
Term
|
Definition
| RAG 1 / 2 performs a single stranded nick at the exact 5' border of the heptameric HSS bordering both V and J segments. |
|
|
Term
| Step three of recombination |
|
Definition
| The hydroxyl group (HO) attacks the phosphate group on the noncoding strand of the V segment to yield a covalently-sealed hairpin coding end and blunt signal end. |
|
|
Term
| Gene rearrangement occurs in ____prior to gene transcription into mRNA. |
|
Definition
|
|
