Lymphocyte receptor development and antigen receptor gene rearrangement

Question 1

At what stage in development does a B cell begin DH to JH rearrangement?

Answer 1

Pro-B cell

Question 2

At what stage in development does a B cell complete VJ rearrangement for kappa and/or lamba chains?

Answer 2

Immature B cell

Question 2

At what stage in development does a B cell complete VH to DJH rearrangement?

Answer 2

Pre-B cell

Question 3

At what stage in development does a B cell begin to express IgM?

Answer 3

Immature B cell

Question 4

At what stage in development does a B cell begin to express IgD?

Answer 4

Mature B cell

Question 4

Which surface marker(s) are present on B stem cells?

Answer 4

CD43+

Question 5

Which surface marker(s) are present on pro-B cells?

Answer 5

CD43+, CD19+, CD10+

Question 6

Which surface marker(s) are present on pre-B cells?

Answer 6

B220lo, CD43+

Question 7

Which surface marker(s) are present on mature B cells?

Answer 7

IgM+ and IgDhi

Question 7

Which surface marker(s) are present on immature B cells?

Answer 7

IgM+, CD43-

Question 8

At what stage in development does a T cell begin DB to JB gene rearrangement?

Answer 8

Pro-T cell

Question 9

At what stage in development does a T cell complete Va to Ja gene rearrangement?

Answer 9

Double positive T cell

Question 9

At what stage in development does a T cell complete VB to DJB gene rearrangement?

Answer 9

Pre-T cell

Question 10

At what stage in development does a T cell begin to express aB TCR?

Answer 10

Double positive T cell

Question 11

Which surface marker(s) are present on T stem cells?

Answer 11

c-KIT+
CD44+
CD25-

Question 12

Which surface marker(s) are present on pro-T cells?

Answer 12

c-KIT+
CD44+
CD25+

Question 13

Which surface marker(s) are present on pre-T cells?

Answer 13

c-KIT+
CD44-
CD25+

Question 14

Which surface marker(s) are present on double positive T cells?

Answer 14

CD4+/CD8+
TCR/CD3lo

Question 15

Which transcription factors are associated with B lineage hematopoiesis?

Answer 15

EBF, E2A, and PAX5

Question 16

Which transcription factors are associated with T lineage hematopoiesis?

Answer 16

Notch 1 and GATA3

Question 17

Which transcription factors are associated with innate lymphoid cell hematopoiesis?

Answer 17

Id2

Question 18

What are the components of the pre-BCR?

Answer 18

u heavy chain, invariant surrogate light chains (v pre-B protein and lamba5 protein), and signal-transducing Iga and IgB

Question 19

What are the components of the pre-TCR?

Answer 19

TCR B chain, invariant pre-T alpha (pTa) chain and signal-transducing CD3 and zeta proteins

Question 20

What are the signals propagated by the pre-BCR?

Answer 20

1. Proliferation of pre-B cells
2. Inhibition of H chain recombination (allelic exclusion)
3. Stimulation of kappa light chain recombination
4. Shut off surrogate light chain transcription

Question 21

What are the signals propagated by the pre-TCR?

Answer 21

1. Proliferation of pre-T cells 2. Inhibition of B chain gene recombination 3. Stimulation of alpha chain rearangement 4. Shut off pre-Ta chain transcription 5. Expression of CD4 and CD8

Question 22

What is the pathophysiology of X-linked agammaglobulinemia?

Answer 22

Mutations in Bruton tyrosine kinase prevent delivery of signals from BCR that mediate survival, proliferation and maturation beyond the pre-B cell stage.

Question 23

What is somatic hypermutation?

Answer 23

High frequency point mutations in Ig heavy and light chains that occur in germinal center B cells in response to signals from Tfh cells. It is present in B cells only. Mutations are clustered in V regions, mostly in CDRs.

Question 24

Which enzyme mediates somatic hypermutation?

Answer 24

AID

Question 25

What is receptor editing?

Answer 25

Inducement of further Ig gene rearrangements in strongly self-reactive immature B cells

Question 26

Which enzyme in the thymus induces expression of self antigens usually only expressed in specific peripheral organs?

Answer 26

autoimmune regulator (AIRE)

Question 27

What is the end result of positive selection of T cells?

Answer 27

Cells with TCRs that recognize MHC Expression of coreceptor (CD4 , CD8) complementary to MHC recognized

Question 28

What is the end result of negative selection of T cells?

Answer 28

Elimination of cells with high affinity for self antigens (clonal deletion)

Question 29

What is the end result of positive selection of B cells?

Answer 29

Cells with functional BCRs

Question 30

What is the end result of negative selection of B cells?

Answer 30

Induction of further Ig gene rearrangements in self-reactive cells Elimination of cells whose rearrangements continue to contribute to formation of self-reactive cells (clonal deletion)

Question 31

Where do positive and negative selection of B cells occur?

Answer 31

Bone marrow

Question 32

Where does positive selection of T cells occur?

Answer 32

Thymic cortex

Question 33

Where does negative selection of T cells occur?

Answer 33

Thymic medulla

Question 34

In which order do positive and negative selection of B and T cells occur?

Answer 34

Positive selection occurs first, followed by negative selection

Question 35

What are the four steps of VDJ rearrangement?

Answer 35

1. Synapsis 2. Cleavage 3. Hairpin opening and end-processing 4. Joining

Question 36

Describe synapsis in V(D)J recombination.

Answer 36

Coding segments and adjacent recombination signal sequences (RSSs) brought together by chromosomal looping event

Question 37

Describe cleavage in V(D)J recombination.

Answer 37

V(D)J recombinase (RAG1 and RAG2) creates double stranded breaks at RSS-coding sequence junctions.

Question 38

Describe hairpin opening and end-processing in V(D)J recombination.

Answer 38

ARTEMIS opens hairpins. Terminyl deoxynucleotidyl transferase (Tdt) adds nucleotides to broken DNA ends.

Question 39

Describe joining in V(D)J recombination.

Answer 39

DNA-dependent protein kinase (DNA-PK) and DNA ligase join segments together.

Question 40

Describe the 12/23 rule.

Answer 40

Recombination only occurs between two segments if one segment is flanked by a 12-nucleotide spacer and the other by a 23-nucleotide spacer. 12- and 23- nucleotide spacers correspond to 1 or 2 turns of a DNA helix and ensure that two RSSs are brought close to each other for recombination.