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IMMUNOLOGY > Lecture 12+13: B cells > Flashcards

Lecture 12+13: B cells Flashcards

1
Q

what orchestrates the development of lymphocytes

A

stromal cells and cytokines

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2
Q

what are lymphocytes (B cells, T cells and NK cells) derived from

A

Hematopoietic stem cells —> multipotent progenitor cells —> common lymphoid progenitor cells —-> lymphocytes

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3
Q

antibody secreting plasma cells…AKA?

A

effector B cells

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4
Q

adaptive humoral immunity mostly works against ?

A

extracellular microbes and their products

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5
Q

what are the 2 classes of B cells

A

B-1 : Primarily mature in fetal liver, can self renew

Follicular B-2 cells: mature in the bone marrow

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6
Q

what is the physical composition of B cells

A

4 peptide chains joined by disulfide bonds
- 2 identical heavy chains
- 2 identical light chains
– each w/ variable and constant regions

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7
Q

what ligand does the transmembrane region of the B cell interact w/ for signaling

A

CD79 (Igα + Igβ)

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8
Q

where does B cell development occur

A

bone marrow

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9
Q

what cells direct the development of B cells in the bone marrow

A

Stromal cells

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10
Q

the rearrangement of Ig genes starts w/ ?

A

rearrangement of the heavy chain

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11
Q

early pro-B cell phase starts with what rearrangement

A

D-J rearrangement of heavy chain

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12
Q

late Pro-B cell development phase continues with what rearrangement

A

V-DJ

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13
Q

blocking what step in B cell development would prevent further development

A

large pre B cell

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14
Q

what is allelic exclusion?

A

ensures B cell expresses only one receptor type

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15
Q

why is it important that B cells don’t make more than one type of BCR

A
  • it would be detrimental to immune response
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16
Q

what is X-linked agammaglobulinemia (XLA)

A
  • mutation in BTK
  • characterized by a lack of B cells and serum antibodies

BTK = important kinase in signal transduction from pre-B cell receptor
- BTK mutation cannot transmit the signal for proliferation and differentiation of pre-B cells
- results in apoptosis of the pre-B cell

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17
Q

what does the Lare Pre-B cell step check for

A
  • checks for functional heavy chain
  • checks for compatibility w/ surrogate light chain
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18
Q

rearrangements of the light chain starts with …..?

A

kappa
use of lamba is done to increase the odds of a successful rearrangement

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19
Q

what does combinational diversity depend on

A

which V, D and J segments are used in the development of the BCR allele

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20
Q

what is junctional diversity

A

during splicing, has to do with which specific nucleotides are added or deleted

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21
Q

what type of surface receptor do immature B cells make

A

only IgM

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22
Q

what occurs during receptor editing

A
  • a chance to save the self-reactive B cells
  • VJ rearrangements on the light chain can occur
  • light chain editing only (kappa followed by lambda)
  • new light chain and new IgM made
  • once again goes through negative selection process
  • heavy chain remains
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23
Q

what occurs after immature B cells make it past negative selection

A

alternative RNA splicing of the primary RNA transcription occurs in B2 cells

  • this produces two different mRNAs
  • VDJ region combined w/ mu constant region
  • VDJ region combined w/ delta constant region
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24
Q

what allows B2 cells to be able to synthesize both IgM and IgD

A

alternative RNA splicing

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25
Q

what is the half life of mature B cells

A

100 days

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26
Q

what are the stages of B cell development?

A

Progenitor (Pro-B cell)
Precursor (Pre-B cell)
Immature B cell
Mature, naive B cell

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27
Q

in what stage does the initial expression of CD19 and CD20 occur along with initiation of somatic recombination of the heavy chain

A

pro B cell

28
Q

in what stage does the initiation of somatic recombination of the light chain occur

A

Pre-B cell

29
Q

at what stage of B cell development does negative selection occur

A

immature B cell

30
Q

what are the antigen-dependent phases of B cell development

A

B cell activation
B cell differentiation

31
Q

what are T-dependent antigens

A

protein antigens that lead to B cell activation w/ helper T cells

32
Q

what are T-independent antigens

A

non-protein antigens that lead to B cell activation w/out helper T cells

33
Q

where are B1 B cells located

A

in mucosal tissues and pleural/peritoneal cavities

34
Q

what type of antigens do B2 B cells mostly respond to

A

T-dependent antigens

35
Q

what type of antigens do B1 B cells mostly respond to

A

T-independent antigens

36
Q

where do B cells circulate

A

between blood and lymphoid tissues to find antigens

37
Q

what attracts follicular B cells to follicles

A

by B cell-specific chemokines produced by follicular dendritic cells (FDCs)

38
Q

what happens if follicular B cells don’t get activated in the follicles

A

they leave following the S1P gradient

39
Q

how do antigens enter the secondary lymphoid organs from the lymph/blood

A

by crossing epithelial barriers or by being carried in via DC cells to interact w/ receptors on the follicular B cells

40
Q

what is the first signal in B2 (follicular) cell activation

A

follicular B cells are initially activated upon antigen binding to the BCR

for signal transduction, aggregation of receptors is needed to induce proliferation

41
Q

how can aggregation of receptors occur

A
  1. antigen binding and cross linking 2 or more BCRs
  2. antigen cross-linking a BCR with the CR19/CD21 coreceptor
42
Q

once follicular B2 cells are activated by the first signal where do they migrate to

A

the outer edge of the follicle into the T cell zone

43
Q

B2 cells receive their second signal from what cells

A

Th cells and Th cell cytokines (CD40, CD40L)
- IL4 induces the proliferation of Th cytokines

44
Q

If B cells have a strong reaction to self during negative selection, what are the 4 possible fates

A
  1. clonal deletion
  2. receptor editing
  3. anergy
  4. immunologic ignorance
45
Q

what is clonal deletion?

A

apoptosis of B cells that have a high affinity for self-antigen

46
Q

what is receptor editing?

A

further genetic rearrangement to replace BCR with one that doesn’t self-react

47
Q

what is anergy?

A

a permanent state of unresponsiveness, eventually leads to death

48
Q

what is immunological ignorance?

A

cells have an affinity for self-antigens but don’t respond to them

49
Q

what percent of immature B cells have some affinity for self

A

about 75%
- they get sent for receptor editing

50
Q

during receptor editing, V- J rearrangements occur on what chain

A

light chain

51
Q

what stage of B cell development is characterized by the initial expression of CD19 & CD20

A

Pro-B cell

52
Q

what stage of B cell development is characterized by the successful recombination and expression of the heavy chain as a Pre-BCR

A

Pre-B cell

53
Q

what stage of B cell development is characterized by successful recombination and expression of a membrane-bound BCR complex

A

Immature B cell

54
Q

what stage of B cell development does negative selection occur

A

Immature B cell

55
Q

Non-protein antigens that lead to B cell activation without helper T cells

A

T-independent B1-B cells

56
Q

where does the 2nd signal for B-cell activation come from

A

the interaction of the B cell with Th cell and Th cell cytokines

57
Q

what occurs in the germinal center reaction

A

follicular B cells interact w/ follicular dendritic cells and follicular helper T cells

  • class switching from IgM —> another isotope
  • affinity maturation = mutations increase binding affinity of antibodies to target
57
Q

what is extrafollicular focus

A

A subset of the follicular B cells differentiate rapidly into antibody-producing plasma cells
* Located outside of follicle = extrafollicular focus
* Short-lived plasma cells producing low affinity IgM

58
Q

after undergoing class switching and affinity maturation in the germinal center reaction, what happens to B cells

A

they differentiate into effector and memory cells

59
Q

class switching is directed by?

A

Tfh interaction via CD40-CD40L

60
Q

what immunoglobulin does IL-4 induce

A

IgE

61
Q

what immunoglobulin does INF-y induce

A

IgG

62
Q

what immunoglobulin does TGF-B induce

A

IgA

63
Q

what is AID

A

an enzyme, Activation-induced cytidine deaminase

functions by intentionally introducing mutations that must be repaired

64
Q

can plasma cells present antigens

A

no b/c they cannot express MHC class II or co-stimulatory molecules

they are entirely committed to making antibodies

65
Q

activation of memory B cells is what kind of immune response

A

secondary

IMMUNOLOGY (26 decks)

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