VDJ B cell recombination Flashcards
as B cells proliferate following ANTIGEN CONTACT at secondary LYMPHOID ORGANS, mutations occur PREFERENTALLY in the VDJheavy and VJlight genes, this process if called….
somatic hypermutation
B cells at secondary lymphoid organs who are trying to figure what’s the antigen binding site they should have, mutates its antigen binding sites, if these altered ab failed to bind antigen……
B cell dies
B cells at secondary lymphoid organs, if they mutate their antigen binding sites that bind antigen better than the original, these B cells….
receive stronger signals to proliferate and mature into PLASMA CELLS
As immune reponse progresses, the average affinity of the responding B cells and antibody produced in 2NDARY LYMPHOID ORGANS…….
INCREASES this is called AFFINITY MATURATION
Isotype switching increases the………of ab molecules
FUNCTIONAL DIVERSITY
Isotype switching deals with the ……of the ab, where as somatic hypermutation invovlves…….
ISOTYPE FUNCTIONAL DIVERSITY
SOMATIC HYPERMUTATION mutating its antigen binding sites of Ig to increase the ab affinity to the antigen its presented to
When does isotype switching occur……
occurs following ANTIGEN stimulation and TH2 cytokine production
List CH genes in linear order
C mu, C delta, C gama3, Cgama1, PSEUDOGENE C epsilon, C alpha 1, C gama 2, Cgama 4, Cepsilon, and Calpha 2
Each C gene segment except….. is preceded by an intron containg a ……sequence
C delta
SWITCH REGION
Switch sequences differ from recombination signal sequences found flanking V regions seg
True
switch sequences introns, don’t code for nonsense
in vdj you can get nonsense nonfunctional parts
Rearranged VDJHeavy is always expressed……with membrane…..
FIRST…Cmu or IgM
Mature B celll has…
BOTH MEMBRANE C(mu) and C(delta)
As B cell begins to respond to antigen it secretes……
SECRETED C mu IgM
What causes B cells to switch isotopes…..
receiving CYTOKINES
The DNA between two switch regions that are recobminating are…..
lopped out and removed from genome
All…..are productive since DNA spllicing occurs w/in ……so non nonsense codons are NOT introduced into the transcribed DNA
PRODUCTIVE
SPLICING OCCURS in INTRONS
Further switches to down stream isotypes IgA and IgE may occur if the B cell receives the required…..
cytokine signal
Genes for ig are UNLIKE other human genes in that
a) each polypeptide chain is encoded by several exons.
b) Ig genes are composed of introns and exons
c) somatic recombination occurs before mRNA is transcribed
d) there is less Ig genetic material in mature B cells than in other somatic cells
c) somatic recombination occurs before mRNA is transcribed
d) there is less Ig genetic material in mature B cells than in other somatic cells
Somatic recombination results in loss of DNA.
CH (Cheavy) affects the……but not the…..
biological functions but NOT antigen-binding specificity of the ab
Which does NOT contribute to Ig antigen-binding diversity
a. Any L chain can combine with any H
chain to form a functional antibody.
b. Any Vk can be joined to any Jk to encode the light chain V region.
c. Many CH genes are present in the germline DNA.
d. Random numbers of N nucleotides can be added during somatic recombination.
e. VJL and VDJH joining is imprecise.
c. Many CH genes are present in the germline DNA.
List 4 things that contribute to Ig ANTIGEN BINDING DIVERSITY
Any L chain can combine with any H
chain to form a functional antibody.
Any Vkappa can be joined to any Jkappa to encode the light chain V region.
Random numbers of N nucleotides can be added during somatic recombination.
VJL and VDJH joining is imprecise.
The proper joining of one VL to one JL is regulated by…..
12 and 23 nucleotide spacers between heptamer and nonamer sequences.
Clonal selection is the…..
availability of a mechanism to focus the antigen to the appropriate B cells and enable the stimulation of those B cells
Most cells of the vertebrate species have a diploid chromosomal organization and express both alleles of an active gene. The ….. are an exception to this rule because only ONE of their alleles is expressed as a FUNCTIONAL product.
Ig and TCR
Since each B cell productively rearranges a single H and L chain allele, it exhibits
a. affinity.
b. allelic exclusion
c. antibody restriction.
d. antigen-binding diversity.
e. cross-reactivity
b. allelic exclusion
Productively rearranging only one H and one L chain means that a single B cell makes antibodies with only one allotype and one antigen-binding specificity.
B cells must express an …..before they can mature and leave the marrow.
antigen receptor
where they travel to lymph nodes to meet antigens, and are activated go to the germinal centers and proliferate. Once they become plasma cells, they go back to the bone marrow.
Somatic recombination occurs
a. in the bone marrow stem cell.
b. in the progenitor cell as it is becoming a B cell.
c. in the mature B cell following antigen contact.
d. in the plasma cell after antigen contact.
e. in the plasma cell after antibody secretion.
b. in the progenitor cell as it is becoming a B cell.
the reason why its not a is because it said stem cell, stem cell which is incorrect
Somatic recombination occur prior to the B cell coming in contact with antigen, occurs in the bone marrow
once B cells have their BCR and are matured,naive B cells
they travel to the secondary lymphocytes and interact with their antigens and T helper cells, then they go to germinal centers to proliferate and differentiate
once they are plasma cells they return to their bone marrow
Plasma cells are effector cells and actually express little…..
MEMBRANE IG
Diversity comes from many different antigen-binding sequences; each B cell expresses
ONLY ONE
Cross-reactivity depends on
two antigens having similar epitopes, not on somatic recombination.
Isotype switching
a. changes the leader sequence exon so the antibody is secreted.
b. improves the antigen binding specificity of an Ig molecule.
c. increases the affinity of antibodies in a process called affinity maturation.
d. increases the functional diversity of Ig molecules.
e. occurs randomly between switch regions.
d. increases the functional diversity of Ig molecules.
Secretion versus membrane-bound Ig depends on which
CH exons are in the final message.
Different isotypes have different biological functions but they can have the same
antigen-binding specificity.
Isotype switching occurs at switch sites and is regulated by
helper T cell cytokines along with their cytokines to tell the B cell to secrete what kind of ab
Isotype switching resembles somatic recombination because both processes
a. are catalyzed by the products of RAG1 and RAG2
b. are regulated by helper T cell cytokines.
c. can result in stop codons in coding sequences.
d. occur in developing B cells in the bone marrow.
e. result in the irreversible loss of DNA from the B cell.
e. result in the irreversible loss of DNA from the B cell.
Both processed result in looping out of DNA.
Rag-1 and RAG-2 products catalyzes
antigen binding specificity
T cell cytokines do not…..
Regulated somatic recombination
since somatic recombination occurs prior to B cell meeting the antigen, engulfing, and presenting it as an APC for a T helper cell come along bind to it and secrete the necessary cytokines for the B cell differentiate into a plasma cell and start secreting high affinity antibodies
Splicing between gene segments is imprecise, sometimes resulting in nonproductive rearrangements in which
frame shift mutations yield stop codons downstream and no complete H or L chain can be produced.
Products of what genes are required for somatic recombination
two recombination-activating genes, RAG-1 and RAG-2
enzymes to ligate (reattach) the DNA
terminal deoxynucleotidyl transferase (TdT)
Junctional diversity affects primarily the amino acid sequence in
a. all CDR equally.
b. CDR1.
c. CDR2.
d. CDR3.
e. FR3.
d. CDR3.
Only ……..can be produced simultaneously. ………require isotype switching during which exons for mu and delta are lost. Select another answer.
IgM and IgD can be SIMULTANEOUSLY produced
IgG, IgA, and IgE need ISOTYPE SWITCHING
Alternative mRNA splicing occurs
> IMMATURE B CELLS
> IN BONE MARROW
> W/OUT T CELL HELP
.Alternative mRNA splicing
a. allows the B cell to improve its antigen-binding fit after antigen contact.
b. allows the B cell to make membrane IgM from the mature mRNA for secreted IgD.
c. can be used for the simultaneous production of any two Ig isotypes.
d. is a process by which a B cell can simultaneously synthesize m and d chains.
e. occurs in response to T cell cytokines.
d. is a process by which a B cell can simultaneously synthesize m and d chains.
Because of the order of the CH gene segments (Cm, Cd, Cg3, Cg1, pseudogene Ce, Ca1, Cg2, Cg4, Ce, and Ca2), a human B cell which undergoes isotype switching from IgM to IgG1 can never in the future secrete
a. IgA.
b. IgE.
c. IgG2.
d. IgG3.
e. IgG4.
d. IgG3.
The gamma 3 exon is upstream from gamma 1 and is lost in the isotype switch.
Gene recombination and DNA loss is part of isotype switching.
True
DNA between the former CH and the new CH is lost.
True
B cells can only produce…and… simultaneously.
IgM and IgD
via alternate splicing
other antibodies IgE, IgG, IgA have to undergo isotype switching
Isotype switching is always productive because
a. B cells produce all isotypes simultaneously.
b. isotype switching does not involve recombination of DNA gene segments.
c. no DNA is deleted from the chromosome in isotype switching.
d. no effector diversity results from isotype switching.
e. recombination between switch sites occurs in introns so it cannot introduce stop codons into coding regions.
e. recombination between switch sites occurs in introns so it cannot introduce stop codons into coding regions.
which is different from the VDJ/VJ variable binding regions where stop condons do occur in exons and results in a non-functional
Many B cells undergo unfavorable mutations and
die because they can no longer bind antigen.
Somatic hypermutation
1) occurs during B cell proliferatioin
2) occurs in B cell FOLLOWING antigen stimuation
3) result in increased affinity of ab secreted later in immune responses
4) result in death of some B cells which non longer bind antigen
Somatic hypermutation…. in the B cell which has bound antigen.
does occur
- IMPORTANT
Somatic Recombination is NOT THE SAME AS somatic hypermutation in that.
> somatic recombination occurs PRIOR to antigen contact, during B cell development in BONE MARROW
> somatic HYPERMUTATION generates Ig diversity AFTER B cell has matured and migrated to the SECOND LYMPHOID ORGANS
- as B cells proliferate follwing antigen contact, mutations occur PREFERENTIALLY in VDJ, and VJ
In which of the following ways does the developmental pathway of α:β T cells differ from that of B cells? (Select all that apply.)
a. Their antigen receptors are derived from gene rearrangement processes.
b. When the first chain of the antigen receptor is produced it combines with a surrogate chain.
c. Cells bearing self-reactive antigen receptors undergo apoptosis.
d. MHC molecules are required to facilitate progression through the developmental pathway.
e. T cells do not rearrange their antigen-receptor genes in the bone marrow.
d. MHC molecules are required to facilitate progression through the developmental pathway.
e. T cells do not rearrange their antigen-receptor genes in the bone marrow.
they rearrange them in the THYMUS
Which of the following is the first stage of T-cell receptor gene rearrangement in α:β T cells?
a. Vα→Dα
b. Dα →Jα
c. Vβ→ Dβ
d. Dβ→Jβ
e. Vα→Jα.
d. Dβ→Jβ
______ of thymocytes is necessary to produce a T-cell repertoire capable of interacting with self-MHC molecules.
a. positive selection
b. negative selection
c. apoptosis
d. receptor editing
e. isotype switching.
a. positive selection
T-cell receptor binds strongly to self-peptides presented by self-MHC molecules,the thymocyte will be ……selected.
NEGATIVELY
T-cell who don’t recognize MHC molecules of the thymic epithelium will result in ….selection
POSTIVE