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Flashcards in 60-B Cell Development Deck (43)
1

B cell development

from hematopoietic stem cell

2

commitment to B cell lineage

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

3

b cell maturation

bone marrow

4

Fetal development of b cell

liver to spleen to bone marrow

5

clonal representation

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

6

central tolerance

mature b cells are purged of self reactivity

7

VDJ recombination

heavy chain at pro b cell stage

8

VJ recombination

light chain at pre b cell stage

9

allelic exclusion

only 1 successful VDJ and VJ chain recombination is allowed
ensures only 1 unique BCR per B cell clone

10

goal of recombination

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

11

heavy chain

VDJ and constant
chromosome 14

12

kappa light chain

VJ and constant
chromosome 2

13

lambda light chain

V and JC pairs, up to 7, only 4 functional
chromosome 22

14

productive rearrangement

in frame contiguous
successful recombination

out of frame shifts reading frame

15

Heavy chain recombination

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

16

steps in recombination

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

17

end product of VDJ recombination

mu heavy chain protien
defines cell as now being pre B cell

18

proteins made by pre b cell

surrogate light chain complex, made of VpreB and lambda 5

19

pre b cell complex

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

allelic exclusion for VDJ

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

non productive VDJ at both b cell

cannot develop and dies

22

allelic exclusion at light chain

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

non productive at both kappa

lambda loci now open

24

non productive at both lambda

cell dies

25

complete BCR

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

26

recombinatorial diversity

random association of VDJ or VJ

27

junctional diversity

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

recombination is unbiased

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

29

3 outcomes of central tolerance

apoptosis
anergy/cell paralysis
positive selection

30

apoptosis purging

high affinity for self, strong BCR signal, apoptosis

31

cell anergy purging

low affinity for self, modest BCR signal, paralysis

32

positive selection purging

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

33

B1 B cells

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

B2 B cells

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

35

marginal zone b cells

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

36

follicular b cells

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

37

B1 B cell reproduction

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

38

function of B1 B cells

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

39

marginal zones

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

follicular zones

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

distinct zones in SLO

segregation of T and B cells driven by chemokines

42

B cells migrate to?

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

43

T cells migrate to?

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