Lymphocyte Dev. & Ag Receptor Gene Rearrange Test II

Question 1

Maturation of B and T cells occurs in Generative Lymph organs what are the events?

Answer 1

Commitment of progenitor cells to B or T lineage.

Proliferation of progenitors and immature lymphocytes.

Sequential and ordered Rearrangement of Ag receptor genes and expression of BCR or TCR proteins.

Selection events, delete self reactive cells

Differentiation of B and T cells into functionally and phenotypically distinct cells.

Question 2

What can Pro-B cells differentiate into?

Answer 2

FO B cells
MZ B cells
B1 cells

Question 3

What can Pro-T cells differentiate into?

Answer 3

aB T cells
yDelta T cells
NK cells

Question 4

In the Thymus and Bone marrow stromal cells produce ____ which drives proliferation of T cell progenitors and stimulates B cell development.

Answer 4

IL-7

Question 5

Development of NK cells occurs in the thymus and depends on what cytokine?

Answer 5

IL-15

Question 6

In the early commitment to B cells lineage what is the first thing that occurs?

Answer 6

The Ig heavy chain locus opens up and is available to proteins tha mediate Ig gene rearrangement and expression.

Question 7

What TF commit developing lymphocytes to the T cell lineage?

Answer 7

Notch-1 and GATA-3

Question 8

What TF induce edxpression of genes needed for B cell development?

Answer 8

E2A and Pax-5`

Question 9

Describe Allelic Exclusion.

Answer 9

L and H chains of Ig are codominantly inherited and only one of the light and heavy chain alleles can be expressed in a single B cell. Rearrangement of maternal and paternal alleles starts simultaneously but expression depends on which set finishes first and that one will be expressed.

Question 10

What determines variable regions of chains in B and T cell receptors?

Answer 10

Rearrangement of DNA. This includes deletions of DNA/RNA nucleotides and reannealing of the segments, through Rag1 and Rag2 recombination enzymes.

Question 11

What re the three mechanisms of Receptor diversity?

Answer 11

Somatic Recombination
mRNA splicing
Junctional diversity

Question 12

Explain how Rag1 and Rag2 work.

Answer 12

Rag 1 and Rag 2 initiate V(D)J recomb by indroducing double stranded breaks in DNA. Rag mediated breaks are resolved by NHEJ.

Question 13

What does recombination of B cells start with?

Answer 13

Heavy chain in B cells (Beta chain in T cells). If the recombination is functional the rearrangement of light chain K or L occurs in B cells. (alpha chain in T cells)

Question 14

How is BCR diversity achieved?

Answer 14

First D and J are randomly chosed and DNA between is deleted.

Second, a V segment is chosen and DNA between V and DJ is deleted.

Third, C is chosen and DNA between VDJ and C is deleted.

Chances of producing a fxnl rearrangenment is 10% there will be a test for productive rearrangement and once thats confirmed competition between maternal and paternal H chains is over recombination is stopped.

Question 15

What does TdT do?

Answer 15

Adds or removes nucleotides to exposed ends of V D or J genes before they are reunited. It further increases the diversity of TCR and BCR’s

Question 16

Junctional Diversity results from the loss and addition of what?

Answer 16

Loss of nucleotides through exonucleases and addition of N and P nucleotides

Question 17

During lymphocyte development cells go through multiple checkpoints for selection what are they?

Answer 17

1. after produciton of first polypeptide chain of 2chain
   Ag receptor is complete.
2. Follows production of second polypeptide chain the Ag receptor is completed

Checkpoints ensure that only lymphocytes that are successful in Ag receptor rearrangement can mature

Question 18

Pre-BCR’s contain what chain?

Answer 18

IgM heavy chain

Question 19

Pre-TCR’s contain what chain?

Answer 19

TCR B chain

Question 20

What is the first Ag receptor gene to be completely rearranged in B cells?

Answer 20

Ig heavy chain. Once this is successfully rearranged they express IgM heavy chain and assemble pre-BCR

Question 21

If cells make out of frame rearrangements what happens?

Answer 21

They dont receive survival signals and undergo apoptosis

Question 22

If B cells have high affinity for self Ags after first rearrangement what happens?

Answer 22

They undergo the second attempt in gene rearrangement called receptor editing. If editing fails the second time then the B cells die.

Question 23

What kind of B cells do B cells that develop from the fetal liver differentiate into?

Answer 23

B-1 Lineage

Question 24

B lymphocytes that arise from bone marrow precursors after birth give rise to what lineage?

Answer 24

B-2 lineage

Question 25

Why is there no junctionanl diversity in B 1 cells?

Answer 25

TdT is not expressed in the fetal liver and TdT results in junctional diversity

Question 26

Where are a large number of B1 cells found?

Answer 26

In the peritoneum and mucosal sites, they are a self renewing population

Question 27

What type of Abs are present without overt immunization?

Answer 27

“Natural Antibodies”. B1 cells spontaneously secrete IgM that interacts with polysaccharides and lipids and oxidizes them. B1 contribute to most of serum IgM at initial infection

Question 28

What do immature B2 cells differentiate into?

Answer 28

MZ B cells: abundant in spleen can be found in LN too

FO b-2 cells: recirculating lymphocytes

Question 29

What do MZ B cells do?

Answer 29

localize to spleenic marginal zone and respond to blood borne Ags

Question 30

What type of B cell develops into long lived plasma cells or memory B cells?

Answer 30

Only mature FO B-2 cells after T cell dependent activation

Question 31

What B cells are independent of T cell help?

Answer 31

MZ B cells

Question 32

MZ B cells respond to what type of infection, and differentiate into what?

Answer 32

Blood borne microbes and they differentiate into short lived IgM secreting plasma cells

Question 33

About 90% of developing T cells become what type?

Answer 33

aB T cells.

Question 34

Why is there limited diversity of yDelta T cells?

Answer 34

Only a few of the available VdJ segments are used in mature gamma delta T cells