Lymphocyte Development

Question 1

where does B cell development occur?

Answer 1

surface of bone marrow stromal cells

Question 2

what is the survival signal in lymphocytes?

Answer 2

IL-7

Question 3

what genes are part of the Heavy chain of BCR?

Answer 3

VDJ

Question 4

what genes are part of light chain of BCR?

Answer 4

VJ

Question 5

which chains arrange first in BCR assembly

Answer 5

heavy chain variable regions first

Question 6

what directs recombination of the VDJ gene segments in the heavy chain?

Answer 6

recombination recognition sequences (RSS)

Question 7

what does RAG complex do?

Answer 7

cleaves the RRS, recombines the gene segments, and ligates the new segments

Question 8

what is somatic recombination?

Answer 8

during B cell development, areas of VDJ are cut and respliced by DNA recombination

Question 9

what triggers the continuation of somatic recombination?

Answer 9

the successful rearrangement of D-J triggers V-DJ rearrangement

Question 10

what is a pre-B cell?

Answer 10

VDJ of heavy chain has been rearranged, has partial BCR

Question 11

what is allelic exclusion?

Answer 11

only 1 H chain and 1 L chain can be expressed, and the other chromosome locus undergoes epigenetic silencing FOREVER!!!!!!

Question 12

what occurs once H chain is successfully rearranged?

Answer 12

1. other chromosome undergoes epigenetic silencing
2. RAG complex is degraded
3. RAG1 and RAG2 transcription stops
4. large pre-B cells divide to small Pre-B cells and RAG genes are reactivated to produce new RAG complexes for light chain rearrangement

Question 13

what has to occur to result in BCR expression?

Answer 13

successful V-J rearrangement

Question 14

what occurs if kappa L chain genes fail to rearrange?

Answer 14

lambda Light chains attempt to rearrange

Question 15

what gives additional diversity in the Ag binding site of BCR?

Answer 15

addition of random nucleotides at coding joints by TdT ((terminal deoxynucleotidyl transferase)

Question 16

what occurs if either the H or L chains are not produced?

Answer 16

apoptosis

Question 17

describe circulation of B cells after BCR is made

Answer 17

1. self reactive B cells are removed (negative selection)
2. IgM+ immature B cells leave the bone and go to spleen (positive selection)
3. immature B cells access lymph nodes through the high endothelial vessels to become mature B cells

Question 18

what does travel through lymph nodes do to the B cell?

Answer 18

interaction with follicular dendritic cells and cytokines drives maturation (both IgD and IgM expression)

Question 19

how do B cells express both IgM and IgD constant regions

Answer 19

coexpression of IgD and IgM is possible by mRNA alternate splicing

Question 20

where do T cells develop

TCR

Answer 20

thymus

Question 21

what is important about the blood thymus barrier

Answer 21

keeps the environment clear of entering Ag so that T cells can be selected that don’t respond to self

Question 22

what makes up the blood thymus barrier

Answer 22

CTEC and capillary endothelial cell basal lamina, with macrophages between the layers

Question 23

what resides in the thymus cortex?

Answer 23

1. T cells
2. Cortical thymic epithelial cells (CTEC) assist in selecting functional T cells - have MHC I and II that interact with T cells)
3. macrophages
4. blood vessels

Question 24

what resides in the thymus medulla?

Answer 24

1. T cells (not as many)
2. medullary thymic epithelial cells (elimination of self reactive t cells) (negative selection)
3. macrophages
4. dendritic cells to activate Tcells
5. hassalls corpuscles

Question 25

what T cell development step occurs in the thymic subcapsular layer?

Answer 25

double negative (CD4- CD8-_ T cells (Pro t cells) differentiate into pre-T cells expressing 1 rearranged chain of the TCR (beta chain)

Question 26

what is double negative ?

Answer 26

pro-t cell does not have CD4 or CD8 expression

Question 27

what constitutes a pro-T cell?

Answer 27

no CD4 or CD8 expression, no TCR

Question 28

what constitutes a pre-T cell

Answer 28

expresses one rearranged chain of TCR (BETA CHAIN)

Question 29

what TCR chain genes rearrange first?

Answer 29

beta chain genes

Question 30

what promotes alpha chain rearrangement?

Answer 30

successful beta chain rearrangement

Question 31

what does successful rearrangement of both beta and alpha chains trigger?

Answer 31

induces gene expression of BOTH CD4 and CD8 = double positive T cells

Question 32

where do double positive cells occur?

Answer 32

cortex of thymus

Question 33

where does positive selection occur?

Answer 33

cortex

Question 34

what cells are important for positive selection?

Answer 34

CTEC

Question 35

how are DP T cells differentiated to CD4 or CD8?

Answer 35

DP T cells engage CTEC to determine CD4 or CD8, and a significant number of DP T cells apoptose

Question 36

where do differentiated T cells undergo negative selection?

Answer 36

thymic medulla

Question 37

what occurs in the SP (specific) T cells once they travel into the medulla?

Answer 37

TCR signaling molecules are expressed, so they can form response to recognized Ag; they encounter MTEC and DC

Question 38

what does MTEC do?

Answer 38

able to produce most of the protein/peptides (SELF ANTIGENS) found throughout body system -- aka presents self antigens to Tcells to ensure they arent self reactive

Question 39

what do hassal's corpuscles do?

Answer 39

produce TSLP which matures the DC in the medulla so they can better present peptides to SP T cells

Question 40

what occurs to SP T cells that bind strongly to self Ag?

Answer 40

apoptosis (negative selection)

Question 41

what occurs to SP T cells that bind moderately to self Ag?

Answer 41

survive

Question 42

what are the surviving CD4 and CD8 T cells called in the medulla?

Answer 42

naive and mature

Question 43

what does CCR7 signal for?

Answer 43

migration to the secondary lymphoid organs