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Immunology > 60-B Cell Development > Flashcards

60-B Cell Development Flashcards

1
Q

B cell development

A

from hematopoietic stem cell

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2
Q

commitment to B cell lineage

A

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

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3
Q

b cell maturation

A

bone marrow

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4
Q

Fetal development of b cell

A

liver to spleen to bone marrow

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5
Q

clonal representation

A

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

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6
Q

central tolerance

A

mature b cells are purged of self reactivity

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7
Q

VDJ recombination

A

heavy chain at pro b cell stage

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8
Q

VJ recombination

A

light chain at pre b cell stage

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9
Q

allelic exclusion

A

only 1 successful VDJ and VJ chain recombination is allowed

ensures only 1 unique BCR per B cell clone

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10
Q

goal of recombination

A

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

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11
Q

heavy chain

A

VDJ and constant

chromosome 14

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12
Q

kappa light chain

A

VJ and constant

chromosome 2

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13
Q

lambda light chain

A

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

chromosome 22

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14
Q

productive rearrangement

A

in frame contiguous
successful recombination

out of frame shifts reading frame

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15
Q

Heavy chain recombination

A

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

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16
Q

steps in recombination

A

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

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17
Q

end product of VDJ recombination

A

mu heavy chain protien

defines cell as now being pre B cell

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18
Q

proteins made by pre b cell

A

surrogate light chain complex, made of VpreB and lambda 5

19
Q

pre b cell complex

A

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

20
Q

allelic exclusion for VDJ

A

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

21
Q

non productive VDJ at both b cell

A

cannot develop and dies

22
Q

allelic exclusion at light chain

A

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

23
Q

non productive at both kappa

A

lambda loci now open

24
Q

non productive at both lambda

A

cell dies

25
Q

complete BCR

A

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

26
Q

recombinatorial diversity

A

random association of VDJ or VJ

27
Q

junctional diversity

A

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

28
Q

recombination is unbiased

A

BCR recognize self Ags as much as foreign Ags

must purge self reactive immature B cells “central tolerance”

29
Q

3 outcomes of central tolerance

A

apoptosis
anergy/cell paralysis
positive selection

30
Q

apoptosis purging

A

high affinity for self, strong BCR signal, apoptosis

31
Q

cell anergy purging

A

low affinity for self, modest BCR signal, paralysis

32
Q

positive selection purging

A

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

33
Q

B1 B cells

A

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

34
Q

B2 B cells

A

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

35
Q

marginal zone b cells

A

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

36
Q

follicular b cells

A

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

37
Q

B1 B cell reproduction

A

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

38
Q

function of B1 B cells

A

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

39
Q

marginal zones

A 
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
40
Q

follicular zones

A

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

41
Q

distinct zones in SLO

A

segregation of T and B cells driven by chemokines

42
Q

B cells migrate to?

A

follicles, secretion of CXCL13 by dendritic cells

CXCR5 on b cells binds to 13

43
Q

T cells migrate to?

A

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

Immunology (19 decks)

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