Lecture 10

Question 1

What do pluripotent stem cells give rise to?

Answer 1

distinct B and T lineages

Question 2

Hematopoietic stem cells give rise to _____

Answer 2

common lymphoid progenitor (CLP)

Question 3

common lymphoid progenitor (CLP) give rise to what?

Answer 3

B cells, T cells and NK cells

Question 4

What can pro-B cells eventually differentiate into?

Answer 4

FO B cells (follicular)
MZ B cells (marginal zone)
B-1 cells

Question 5

What can pro T cells commit to?

Answer 5

aB T cells
yS T cells
NK cells

Question 6

proliferation of the committed T and B cell progenitors is stimulated by ______

Answer 6

cytokines

Question 7

What does proliferation ensure?

Answer 7

that a large pool of progenitor cells is available for generation of high diversity of mature lymphocytes

Question 8

What happens if a pre-Ag receptor is successfully rearranged?

Answer 8

it provides survival signals that select the cell

Question 9

In the thymus, stromal cells produce ____ that drives proliferation of human ______

Answer 9

IL-7; T cell progenitors

Question 10

____ produced by stromal cells in the bone marrow promotes _____ development at al stages of human life

Answer 10

IL-7, B cell

Question 11

Development of NK cells occurs in _____ and depends on _____

Answer 11

thymus; IL-15

Question 12

What happens first in the early commitment of a developing B cell?

Answer 12

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

Question 13

What happens first in the early commitment of alpha/beta T cell development?

Answer 13

TCR Beta gene locus opens up and becomes accessible to TCR one rearrangement and expression

Question 14

___ and ___ transcription factors commit developing lymphocytes to the T cell lineage

Answer 14

Notch 1 and GATA-3

Question 15

What proteins regulate TCR rearrangement?

Answer 15

Rag-1 and Rag-2

Question 16

What transcription factors induce the expression of genes required for B cell development?

Answer 16

EBF (early B cell factor)
E2A
Pax-5

Question 17

What do Rag-1 and Rag-2 proteins do?

Answer 17

regulate BCR rearrangement

Question 18

What encoding genes are required for B cell development?

Answer 18

Rag-1 and Rag-2
surrogate light chains
IgA and IgB signaling protein of the B cell receptor complex

Question 19

what does epigenetic mechanisms do for genes?

Answer 19

make genes available or unavailable in chromatin

Question 20

Describe euchromatin

Answer 20

loosely packed, genes are available and are transcribed

Question 21

describe heterochromatin

Answer 21

tightly packed, genes are maintained in a silenced state

Question 22

What is gene silencing done by?

Answer 22

non-coding microRNAs

Question 23

how do individuals inherit maternal and paternal sets of alleles for L and H chains of Ig molecule?

Answer 23

codominantly

Question 24

describe allelic exclusion

Answer 24

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

allelic exclusion also governs the expression of TCR

Question 25

how are variable regions of the chains in T and B cells determined?

Answer 25

rearrangement of DNA

Question 26

_______ is the major mechanism of epitope specific diversity of BCR and TCR

Answer 26

DNA chromosomal rearragnemtn

Question 27

How is BCR diversity achieved?

Answer 27

Each B cell generates its own V-D-J sequence, thus making all B cells different

Question 28

When is the expression of RAG-1 and RAG-2 restricted?

Answer 28

When B and T lymphocytes are during their developmental stage

Question 29

What are the steps in achieving BCR diversity?

Answer 29

1. D and J are chosen and Dan between them is deleted
2. V segment is chosen and DNA between V and DJ is deleted
3. C is chosen and DNA between VDJ is deleted
   This is followed by a test for selection of productive rearrangement, and when it is over the competition between paternal and maternal H chain genesis over and recombination of other segments is stopped

Question 30

What occurs in the recombination of the light chain?

Answer 30

k and gamma light chains don’t have D segment, but the recombination rules are the same for Vl chain as for the VH chain

second test of productive rearrangement is done, resulting in B cell only producing one kinda of VH and VL

Question 31

What is junctional diversity?

Answer 31

terminal deoxynucleotidyl transferase (TdT) adds or removes nucleotides to the exposed ends of the V, (D) or J genes before they are reunited

creates a huge variety of TCRs and BCRs

Question 32

Junctional diversity results form the loss of ____ through the action of _____ and from the addition of ____

Answer 32

nucleotides; exonucleases; N and P nucleotides

Question 33

When is the first checkpoint during lymphocyte development

Answer 33

after the production of the first polypeptide chain of the two chain Ag receptor is completed

Question 34

When is the second checkpoint during lymphocyte development

Answer 34

follows production of the second polypeptide chain of the Ag receptor is completed

Question 35

What does positive selection of T cells do?

Answer 35

ensures the maturation of CD8 and CD4 T cells whose receptors don’t recognize self Age but can recognize MHC molecules

Question 36

What does negative selection do?

Answer 36

eliminates harmful T cells and alters harmful B cells whose Ag receptors bind strongly to self antigens present in the thymus or bone marrow

Question 37

Most B cells that develop from the ____ derived stem cells differentiate into B-1 lineage

Answer 37

fetal liver

Question 38

B lymphocytes that arise from ____ precursors after birth give rise to B-2 lineage

Answer 38

bone marrow