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Immunology > B Lymphocyte Development > Flashcards

B Lymphocyte Development Flashcards

1
Q

what is the goal of B cell development

A

generate a diverse antigen receptor - alter or eliminate self-reactive B cells/BCRs - promote foreign reactive B cells to become mature B cells in SLO’s

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2
Q

basic pathway of B cells in the body as they develop and mature

A
  1. generation of BCR in the bone marrow
  2. negative selection in the bone marrow
  3. migration of B cells through the circulatory system to SLO’s
  4. B cell activation in SLO’s
  5. antibody secretion and memory cells made - present in bone marrow and lymphoid tissue
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3
Q

which part of the bone marrow stroma is responsible for secreting growth factors

A

mesenchymal stem cells

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4
Q

what is the order of early stages in B cell development up to an immature B cell

A

primed multipotent progenitor - common lymphoid progenitor - early pro-B cell - late pro-B cell - pre-B cell - immature B cell

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5
Q

which proteins commit the common lymphoid progenitor cell to becoming a B-cell precursor

A

E2A
FOX01
EBF
PAX5

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6
Q

what are the 3 check points in B cell development

A
  1. Large pre-B cell with pre-B receptor
  2. negative selection 1: central tolerance
  3. negative selection 2: peripheral tolerance
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7
Q

which stages of B cell development happen in the bone marrow vs in the SLO’s

A

bone marrow: stem cell to immature B cell
SLO: transitional B cell to mature B cell

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8
Q

which stages of B cell development are antigen-independent vs dependent

A

antigen-independent: stem cell to small pre-B cell
antigen-dependent: immature B cell to mature B cell

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9
Q

why does negative selection 1 create central tolerance?

A

the immature B cell is still in the bone marrow so it is presented with self-antigens

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10
Q

what are the surrogate light chain components in B cell development and when are they present

A

y5 and Vpre-B
present from stem cell to small pre-B cell

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11
Q

what proteins are involved in B-cell development and what are their functions

A

RAG1/2: lymphoid specific recombinase
y5/VpreB: surrogate light-chain components
Kit/IL-7R: growth factor receptor

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12
Q

when does VDJ recombination happen in B cell development

A

D-J rearranging = early pro-B cell
V-DJ rearranging = Late pro-B cell
rearranged = large pre-B cell

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13
Q

when does VJ recombination happen in B cell development

A

V-J rearranging = small pre-B cell
VJ rearranged = immature B cell

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14
Q

appearance of surface Ig in B cell development

A

large pre-B cell: u chain transiently at surface as part of pre-B cell receptor
small pre-B cell: intracellular u chain
Immature B cell: IgM expressed on cell surface
mature B cell: IgD and IgM alternatively spliced H-chain transcripts

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15
Q

what happens if VDJ rearrangement on first and second chromosome of B cell passes vs fails

A

pass = signalled to survive and become pre-B cells
fail = die by apoptosis (about 50%)

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16
Q

Checkpoint #1 of B cell development: pre-BCR testing

A
  • pre-B cell pairs with surrogate light chain to form pre-BCR
  • results in proliferation and progression to L chain rearrangement
  • tests VDJ recombination of only 1 H chain per chromosome (allelic exclusion)
17
Q

is pre-BCR signalling antigen dependent or independent

A

independent

18
Q

what does pre-BCR testing allow?

A

testing of H chain functionality

19
Q

characteristics of the pre-B cell receptor

A
  • inhibition of H chain recombination (allelic exclusion)
  • proliferation of pre-B cells
  • stimulation of k light chain recombination
  • shut off surrogate light chain transcription
20
Q

in gene rearrangement of small pre-B cells what is the order of light chain rearranging

A
  1. rearrange k on 1st chromosome
  2. rearrange k of 2nd chromosome
  3. rearrange y on 1st chromosome
  4. rearrange y on 2nd chromosome
21
Q

what is the first choice of the light chain gene in rearrangement

A

k light chain gene
(y is second choice)

22
Q

checkpoint #2 in B cell development: Negative selection 1

A
  • tests whether VDJ recombination of L chain pairs with H chain to produce a BCR that does not recognize self-antigens
  • L chain exhibits allelic AND isotopic exclusion
  • immature B cell stage
  • happens in central lymphoid organs
  • creates central tolerance
23
Q

what is the difference between L and H chain exclusions

A

L chain = allelic and isotopic exclusion
H chain = only allelic exclusion

24
Q

what is isotopic exclusion

A

Ensures each B cell expresses only one type of light chain (either kappa or lambda), creating uniform antibody structures and further enhancing antibody specificity

25
Q

what is allelic exclusion

A

Ensures that each B cell uses only one allele for the immunoglobulin heavy and light chains, so it produces antibodies with a single specificity

26
Q

binding to self molecules in bone marrow can lead to…

A

receptor editing or death of immature B cells

27
Q

what is receptor editing

A

additional Ig L chain rearrangements give immature B cells in bone marrow additional chances to replace autoreactive BCR with a non-reactive BCR

28
Q

what happens if negative selection 1 or B cells passes vs fails

A

pass = B cell migrates to periphery
fail = receptor editing or apoptosis

29
Q

how does replacement of L chains by receptor editing rescue self reactive B cells

A

it changes its antigen specificity

30
Q

do both B and T cells have receptor editing?

A

NO! only B cells have this

31
Q

brief process of receptor editing

A
  • strong ligation of IgM by self antigen
  • arrest of B-cell development and continues L chain rearrangement leads to low cell-surface IgM
  • new receptor specificity is expressed
32
Q

Checkpoint #3 of B cell development: Negative selection 2

A
  • tests whether BCR with central tolerance fails to recognize any new antigens expressed in the periphery
  • antigen dependent
  • at transitional B cell stage
  • happens in secondary lymphoid organs
  • creates peripheral tolerance
33
Q

what are the differences between negative selection of B cells in bone marrow vs in SLO’s

A
  • in SLO’s, BCR’s that recognize self-molecules cannot undergo receptor editing but ones in BM can
  • only possible outcome in SLO’s is apoptosis of the B cell
34
Q

what are Marginal zone B cells

A

-weakly self-reactive B cells
- high levels of CR CD21
- migrate to marginal zones of white pulp where they make rapid responses to blood-borne pathogens

35
Q

what happens when transitional B cells enter the follicle

A
  • the B cells receive maturation and survival signals which causes them to differentiate into follicular or marginal zone B cells
36
Q

what is BAF

A

a receptor expressed on follicular dendritic cells which stimulates BAFF-R on T1Bs for survival

37
Q

what is the difference between the 2 types of transitional B cells

A

T1B: high IgM, no IgD, BAFF-R, no CD21
T2B: IgM and IgD, BAFF-R and CD21

38
Q

T1 B cells so not have CD21 or IgD and are excluded from the follicle, what will happen to them

A

they will fail to receive maturation and die within 2-3 days of leaving the bone marrow

39
Q

alternative splicing of primary transcripts generates IgM to IgD, at what B cell stage will this happen

A

immature B cell - only IgM
mature B cell - IgM + IgD

Immunology (22 decks)

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