lymphocyte development and antigen receptor gene rearrangement

Question 1

B/T cell maturation

commitment:

TFs responsible for B cell commitment:

TFs responsible for T cell commitment:

Answer 1

activation of TFs shifting to pro-B/T cells

EBF, E2A, Pax-5

Notch-1 and GATA-3

Question 2

B/T cell maturation

proliferation:

Answer 2

simulated by IL-7 in the bone marrow or thymus

Question 3

B/T cell maturation:

selection:

Answer 3

survival of functional receptors that are not self-reactive

Question 4

B/T cell maturation:

differentiation:

Answer 4

diversion into functional subgroups

Question 5

hematopoietic stem cells → _____ → ____ , ____ , and ____

Answer 5

hematopoietic stem cells → common lymphoid progenitor → B cells (in bone marrow), T cells (in thymus), and NK cells (in bone marrow)

Question 6

pro-B cells can eventually differentiate into:

1.

2.

3.

Answer 6

1. FO B cells (follicular)
2. MZ B cells (marginal zone)
3. B-1 cells

Question 7

Pro-T cells may commit to either:

1.

2.

Answer 7

1. alpha-beta T cells
2. gamma-delta T cells

Question 8

commitment to different lineages is driven by

Answer 8

various TFs

Question 9

proliferation of committed T and B cell progenitors is stimulated by

Answer 9

cytokines

Question 10

_____ drives the proliferation of human T cell progenitors in the thymus and promotes B cell development in the bone marrow

Answer 10

IL-7 (produced by stromal cells)

Question 11

the development of NK cells occurs in the ______ and it depends on ______

Answer 11

bone marrow

IL-15

Question 12

early commitment to the B lineage:

first the Ig _____ chain locus opens up and becomes accessible to the proteins that will mediate Ig gene rearrangement and expression

Answer 12

heavy

Question 13

early commitment to the T lineage: (alpha-beta T cells)

first the TCR ____ gene locus opens up and becomes accessible for TCR gene rearrangement and expression

Answer 13

beta

Question 14

DNA methylation on ______ residues generall ______ genes

Answer 14

cytosine

silences

Question 15

the modifications os histone tails of nucleosomes by post-translational _____ , ______ , or _____ render genes either active or inactive

Answer 15

acetylation, methylation, or ubiquitination

Question 16

miRNAs are a class of small noncoding RNAs that control gene expression at the ______ level by impairing translation or by promoting degradation of the mRNA. miRNAs can also accumulate in the nuclei and regualte gene expression at the trascriptional level

Answer 16

post-transcriptional

Question 17

individuals _____ inherit maternal and paternal sets of alleles for L and H chains of Ig molecules

however;

only one of the light chain and heavy chain alleles (either maternal or paternal) is _______ in a single B cell

this is called:

Answer 17

codominantly

expressed

allelic exclusion (similar for TCR)

Question 18

the ______ regions of the chains in T and B cells are determined by rearrangement of the DNA

Answer 18

variable

Question 19

DNA chromosomal rearrangement is the major mechanism of ____ ____ of BCR and TCR

Answer 19

epitope-specific diversity

Question 20

3 mechanisms for BCR and TCR diversity:

1.

2.

3.

Answer 20

1. somatic recombination - V (D) J combination
2. junctional diversity (non-homologous end joining)
3. mRNA splicing

Question 21

BCR/TCR construction:

1. BCR _____ chain and TCR _____ chain made first
2. checks to make sure the first chain was made; _____ chain used
3. BCR _____ chain and TCR _____ chain made second
4. check to make sure that functional _____ chain was made

Answer 21

1. heavy beta
2. surrogate
3. light alpha
4. second

Question 22

BCR/TCR genes:

1. located on chromosome _____
2. B cell heavy chain and T cell beta chains, consist of what segments:
3. B cell light chain and T cell alpha chain, consist of what segments:
4. each segment has multiple copies but all copies except one are _____ giving a unique combination

Answer 22

1. 14
2. (V)ariable, (D)iversity, (J)oining, and (C)onstant
3. (V)ariable, (J)oining, and (C)onstant
4. randomly deleted

Question 23

____ and ____ encode enzymes that perform recombination of BCR and TCR during the process of VDJ recombination

Answer 23

RAG1 and RAG2

Question 24

the cellular expression of RAG1 and RAG2 is restricted to B and T lymphocytes only during their ____ stages

Answer 24

developmental

Question 25

_How is BCR diversity achieved:_ 1. first ____ are chosen and DNA in between them is deleted 2. second ____ segment is chosen and DNA between V and DJ is deleted 3. third a _____ segment is chosen and DNA between VDJ and C is deleted 4. there will be a test for slection of productive rearrangement with help of a: 5. when productive rearrangement is confirmed, the competition between ____ and ____ heavy chain genes is over and the recombination of other segments is stopped

Answer 25

1. D and J segments 2. V segment 3. C segment 4. surrogate light chain 5. maternal and paternal

Question 26

somatic recombination is the process of talking all the copies of the different sements and

Answer 26

choosing only one of each (changes are made to the DNA itself)

Question 27

_Rearrangement occurs in a specific order:_ _BCR heavy chain and TCR beta chain:_ 1. ___ and ___ segments are chosen first, DNA between them is deleted 2. ___ segment is chosen, DNA between it and DJ segment is deleted _BCR light chain and TCR alpha chain:_ 1. ___ and ___ segments are chosen, DNA between them is deleted

Answer 27

_BCR heavy chain and TCR beta chain:_ 1. D and J segments 2. V segment _BCR light chain and TCR alpha chain:_ 1. V and J

Question 28

_mRNA splicing:_ 1. RNA transcript is made from _____ DNA 2. alternative splicing of the ___ segments in BCR result in ____ and ____ variants of BCR 3. this does not apply to ___ , ___ , or \_\_\_

Answer 28

1. recombined 2. C segments IgM and IgD 3. IgG, IgA, or IgE

Question 29

_junctional diversity:_ 1. during rearragement, ___ \_\_\_ ___ are made in the DNA flanking chosen segment 2. DNA strands are ligated via ___ with cosen segments now adjacent to each other 3. new, novel ___ sequences are created

Answer 29

1. double stranded breaks 2. NHEJ 3. DNA

Question 30

what is responsible for most of the diversity in BCR/TCR

Answer 30

junctional diversity

Question 31

\_\_\_ creates asymmetric opening in hair pin loop of DNA

Answer 31

RAG

Question 32

gap between two ends (of cut DNA by RAG) is filled with random, untemplated sequence of nucleotides by \_\_\_

Answer 32

TdT

Question 33

_selection:_ 1. tests to ensure that ____ was actually produced (no out of frame rearrangements) 2. final receptors don't recognize \_\_\_\_ 3. final ___ recognize MHC I/II 4. if any of these fail, cells

Answer 33

1. chain 2. self-Ag 3. TCR do not reeive required survial signals and will die

Question 34

_first selection:_ 1. BCR ___ chain and TCR ___ chain is tested 2. ___ light chain and alpha chain are ued temporarily 3. BCR heavy chain only uses ___ constant region (\_\_) , delta not seen at this time

Answer 34

1. heavy beta 2. surrogate 3. mu (IgM)

Question 35

_second selection_: 1. BCR ___ chain and TCR ___ chain tested 2. BCR heavy chain can use both ___ and ___ constant regions 3. if functional BCR/TCR is made, cell undergoes ____ selection

Answer 35

1. light alpha 2. mu and delta 3. positive/negative selection

Question 36

_positive selection_: 1. completed TCR/BCR does not: 2. TCRs must recognize \_\_\_\_ 3. these cells live on to become:

Answer 36

1. self-Ag 2. MHC 3. immature B/T cells

Question 37

_negative selection:_ 1. completed TCR/BCR recognizes \_\_\_\_\_ 2. self-reactive TCRs undergo: 3. self-reactive BCR undergoes: 4. TCRs that don't recognize ____ are deleted 5. negative selection is responsbile for generating ____ \_\_\_\_

Answer 37

1. self-Ag 2. clonal deletion (by apoptosis) 3. BCR editing 4. MHCs 5. central tolerance

Question 38

_BCR editing:_ 1. BCRs are initially made using the ___ chain 2. if the B cell using the kappa chain is negatively selected, instead of undergoing clonal deletion, it tries again using the ___ chain 3. after the lambda chain is recombined, it goes through the ____ round of selection again 4. if ti fails this time, the B cell undergoes ___ \_\_\_ just like the T cell did

Answer 38

1. kappa 2. lambda 3. second 4. clonal deletion

Question 39

the VDJ rearrangement segment facilitates the synthesis of a ___ or ___ heavy chain controlled by ___ \_\_\_ ___ . this then associates with a light chain, thereby forming an ___ or ___ molecule, which is displayed on the cell-surface of a naive B cell

Answer 39

mu or delta alternative mRNA splicing IgM or IgD

Question 40

\_\_\_ introduces a break in the DNA that is responsible for class-switch recombination to other Ig classes (other than IgM/IgD)

Answer 40

AID (activation-induced cytidine deaminase)

Question 41

AID is only expressed in

Answer 41

activated B cells

Question 42

RAG cleaves ___ and adds ___ nucleotides

Answer 42

hairpin loops P

Question 43

TdT adds ___ nulceotides

Answer 43

N

Question 44

_B-1 cells:_ 1. are made it: 2. no ___ and no ___ diversity 3. reside in: 4. only secrete \_\_\_ 5. ___ population

Answer 44

1. fetal liver 2. no TdT and no junction diversity 3. peripheral tissues 4. IgM 5. self-renewing population

Question 45

_B-2 cells:_ 1. are made in: 2. do have ___ and ___ diversity 3. reside in: 4. can produces all \_\_\_

Answer 45

1. bone marrow 2. have TdT and junctional diversity 3. circuate in blood or reside in lymphoid organs 4. isotypes

Question 46

_B-2 cell subsets:_ 1. 2.

Answer 46

1. FO B cells (follicular B cells) 2. MZ B cells (marginal zone B cells)

Question 47

_FO B cells characteristics:_ 1. 2. 3. 4.

Answer 47

1. circulating population 2. greater diversity, undergo affinity maturation 3. mostly T cell dependent/isotype switched 4. differentiate into long-lived plasma cells OR memory B cells

Question 48

_MZ B cell characteristics:_ 1. 2. 3. 4.

Answer 48

1. located in marginal zone of spleen or LNs 2. less diversity 3. mostly T cell-independent (IgM) 4. differentiate into short lived plasma cells

Question 49

FO B2 cells respond to ____ Ags

Answer 49

protein

Question 50

FO B2 cells, upon T cell dependent activation, develop into

Answer 50

long lived plasma cells or memory B cells

Question 51

similar to B1 cells, MZ B cells have ___ diversity which resopnse to ___ Ags and generate ___ Abs

Answer 51

limited polysaccharide natural

Question 52

while the TCR beta chain is rearranging, the ___ and ___ are also rearranging

Answer 52

gamma chain and delta chain

Question 53

roughly ___ % of developing T cells become gamma/delta T cells

Answer 53

10

Question 54

gamma/delta T cells have very ___ diversity

Answer 54

limited