60-B Cell Development

Question 1

B cell development

Answer 1

from hematopoietic stem cell

Question 2

commitment to B cell lineage

Answer 2

turning on or off transcription factors driven by cytokines and receptor-ligand interactions

Question 3

b cell maturation

Answer 3

bone marrow

Question 4

Fetal development of b cell

Answer 4

liver to spleen to bone marrow

Question 5

clonal representation

Answer 5

each b cell clone expresses many copies of a unique, single BCR

Question 6

central tolerance

Answer 6

mature b cells are purged of self reactivity

Question 7

VDJ recombination

Answer 7

heavy chain at pro b cell stage

Question 8

VJ recombination

Answer 8

light chain at pre b cell stage

Question 9

allelic exclusion

Answer 9

only 1 successful VDJ and VJ chain recombination is allowed

ensures only 1 unique BCR per B cell clone

Question 10

goal of recombination

Answer 10

create diverse set of Vh and Vl regions for antigen binding pocket

Question 11

heavy chain

Answer 11

VDJ and constant

chromosome 14

Question 12

kappa light chain

Answer 12

VJ and constant

chromosome 2

Question 13

lambda light chain

Answer 13

V and JC pairs, up to 7, only 4 functional

chromosome 22

Question 14

productive rearrangement

Answer 14

in frame contiguous
successful recombination

out of frame shifts reading frame

Question 15

Heavy chain recombination

Answer 15

D to J recombination, successful recombination occurs on both chromosomes
V to DJ recombination, successful recombination allowed on only 1 chromosome

Question 16

steps in recombination

Answer 16

elements randomly selected
brought into close proximity with recombinase complex
intervening DNA is cleaved and eliminated
cut DNA ends are ligated

Question 17

end product of VDJ recombination

Answer 17

mu heavy chain protien

defines cell as now being pre B cell

Question 18

proteins made by pre b cell

Answer 18

surrogate light chain complex, made of VpreB and lambda 5

Question 19

pre b cell complex

Answer 19

surrogate light chain binds with mu heavy chain protein to make pre b cell complex expression
block further VDJ recombination and initiate VJ recombination

Question 20

allelic exclusion for VDJ

Answer 20

out of frame DJ for one or both loci
non productive VDJ at one or both loci
pre b cell complex to close other heavy chain

Question 21

non productive VDJ at both b cell

Answer 21

cannot develop and dies

Question 22

allelic exclusion at light chain

Answer 22

transcription and translation of light chains, paired with mu heavy chain and expressed as complete BCR
stops rearrangement at kappa and lambda
stops surrogate light chain production

Question 23

non productive at both kappa

Answer 23

lambda loci now open

Question 24

non productive at both lambda

Answer 24

cell dies

Question 25

complete BCR

Answer 25

pairing of mu heavy chain with light chain to stop all further recombination

Question 26

recombinatorial diversity

Answer 26

random association of VDJ or VJ

Question 27

junctional diversity

Answer 27

open ends of DNA during recombination can be tampered with add nucleic acids using TdT or remove nuclei acids using nucleases makes new coding sequence for Ag binding pocket

Question 28

recombination is unbiased

Answer 28

BCR recognize self Ags as much as foreign Ags | must purge self reactive immature B cells "central tolerance"

Question 29

3 outcomes of central tolerance

Answer 29

apoptosis anergy/cell paralysis positive selection

Question 30

apoptosis purging

Answer 30

high affinity for self, strong BCR signal, apoptosis

Question 31

cell anergy purging

Answer 31

low affinity for self, modest BCR signal, paralysis

Question 32

positive selection purging

Answer 32

lack of Ag binding, no affinity for self, exit to periphery

Question 33

B1 B cells

Answer 33

primitive population, early in ontogeny, fetal derived enriched in serosal lined cavities (pleural and peritoneal), use restricted set of Vh regions express CD19, CD20, IgM and IgD high IgM, low IgD

Question 34

B2 B cells

Answer 34

generated throughout life from bone marrow express CD19, CD20, IgM, and IgD marginal zone and follicular cells

Question 35

marginal zone b cells

Answer 35

reside in spleen t cell independent responses high IgM, low IgD

Question 36

follicular b cells

Answer 36

reside in all secondary lymphoid organs t cell dependent high IgD, low IgM

Question 37

B1 B cell reproduction

Answer 37

self renewal, steady state mitosis creating identical daughter cells to preserve restricted Vh

Question 38

function of B1 B cells

Answer 38

spontaneously differentiate into plasma cells secrete natural Abs (IgM) do not require stimulation from pathogens

Question 39

marginal zones

Answer 39

``` only in spleen border between follicle and red pulp sample blood first coming into spleen appear late in development (2 years) t cell independent responses rapid Ab response against bacteria ```

Question 40

follicular zones

Answer 40

follicles of SLO (spleen, nodes, MALT) present early in life t cell dependent responses and germinal center reaction give rise to memory b cells and long term plasma cells

Question 41

distinct zones in SLO

Answer 41

segregation of T and B cells driven by chemokines

Question 42

B cells migrate to?

Answer 42

follicles, secretion of CXCL13 by dendritic cells | CXCR5 on b cells binds to 13

Question 43

T cells migrate to?

Answer 43

t cell zones, secretion of CCL19 and CCL21 by reticular cells CCR7 on t cells bind to 19 and 21