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B cell development / differentiation upon activation (Exam III) Flashcards

1
Q

B cell development / differentiation

A

T cell dependent interactions

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2
Q

What phases of B cell development are in the BM?

A

Repertoire assembly

Negative selection

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3
Q

What phases of B cell development are in the secondary lymphoid organs and circulation?

A

Positive selection
Searching for infection
Finding infections
Attacking infection

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4
Q

List the B cell development order

A

Repertoire assembly
Negative Selection
Positive selection
Searching for infection
Finding Infection
Attacking infection

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5
Q

Repertoire assembly

A

Generation of clonally expressed B cell receptors in the bone marrow

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6
Q

Negative selection

A

Alteration, elimination or inactivation of B cells receptors that bind to components of the human body

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7
Q

positive selection

A

promotion of a fraction of immature B cells to become mature B cells in the secondary lymphoid tissues

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8
Q

searching for infection

A

recirculation of mature B cells between lymph, blood, and secondary lymphoid tissues

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9
Q

finding infection

A

Activation and clonal expansion of B cells by pathogen derived antigens in secondary lymphoid tissues

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10
Q

attacking infection

A

Differentiation to antibody-secreting plasma cells and memory B cells in secondary lymphoid tissue

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11
Q

Pro B cell stages

A
  1. Early Pro B cell
  2. Heavy chain rearrangement
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12
Q

Pre B cell stages

A
  1. Check point
  2. Light chain rearrangement
  3. Second checkpoint
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13
Q

Immature B cell phase

A
  1. Immature B cell
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14
Q

Early pro B cell

A

commits to B cell lineage

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15
Q

Heavy chain rearrangement

A

Generates heavy chain gene diversity in pro-B cell population

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16
Q

First checkpoint (development of B cell)

A

Selects for functional heavy chains

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17
Q

Light chain rearrangement

A

Generates light chain gene diversity in pre- cell population

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18
Q

Second checkpoint (B cell development)

A

Selects for functional light chains

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19
Q

Immature B cell stage

A

Makes functional IgM

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20
Q

Pre-B cell receptor testing, would be considered to be in what phase of B cell activation?

A

First checkpoint

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21
Q

Second checkpoint

A

functional rearrangement of light chains

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22
Q

what which point is BTK required?

A

first checkpoint - testing of Pre - B cell receptor

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23
Q

Pre B cell receptor (intracellular expression)

A
  • Signals from a properly assembled Pre B cell receptor, induces allelic exclusion at other heavy chain locus
  • surrgoate light chain takes place of rearranged light chain
  • allows for testing of the heavy chain
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24
Q

surrogate light chain composition (PRE-B cell receptor

A
  • VpreB
  • Labmbda 5
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25
Q

B cell receptor surface expression

A

Fully formed B cell receptor has both heavy and light chains

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26
Q

early pro B cell survival

A

H - chain rearrangement
- D-J rearrangement on both chromocomes

(if positive, moves on to late pro B cell phase)

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27
Q

Late pro B cell

A

Heavy chain rearrangement
- V-DJ rearrangement on first chromosome (if positive, signaled to survive and become Pre B cell)
- if ^ didn’t work, V-DJ rearrangement on second chromsome (if positive, signaled to survive and become Pre B cell)

  • If neither worked, signaled to die by apoptosis: 50% of cells
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28
Q

Pre B cell light chain rearrangement order

A
  1. Rearrange K on first chromosome
  2. Rearrange K on second chromosome
  3. Rearrange Lambda on first chromosome
  4. Rearrange Lambda on second chromosome

If any of these worked, cell becomes immature B cells. If not - Apoptosis

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29
Q

As many as _ successive attempts can be made at successful rearrangement of the _ chain

A

5; kappa

between its V-J

30
Q

Immature B cell selection:

A

Immature B cell undergoes Negative selection.

**Still bone marrow **

Receptor editing allows the immature B cell more chances to make a non-autoreactive BCR (editing only in light chain)
Immature B cell continues to rearrange light chain genes

**Immature B cell makes a new light chain and thus an IgM with a different specificity **
- if the new receptor is NOT self-reactive, the B cell leaves the bone marrow.
1. this cell moves into the blood and expresses IgM and IgD, and can search for antigens for activation.
- if the new receptor is self reative, light chain genes continue rearranging.
1. successive new receptors are self reactive. no further rearrangement are possible and the immature B cell undergoes apoptosis

31
Q

Maturation of B cells

A
  • Immature B cells leave the bone marrow and enter circulation, secondary lymphoid organs, and lymph
  • to survive and mature, immature *B cells must enter lymphoid follicles *
  • Interaction with Follicular dendritic cells (FD) provides the required maturation and survival signals - positive selection
  • competition with other B cells is the limiting factor for space in the follicle
32
Q

B cell interaction with Follicular dendritic cells

A

provides the required maturation and survival signals - positive selection.

33
Q

B cell precursors rearrange its immunoglobin genes

A

Generation of B cells receptors in the bone marrow

34
Q

immature B cell bound to self cell surface antigen is removed from the repertoire

A

negative selection in the bone marrow

35
Q

mature B cell bound to foreign antigen is activated

A

migration of B cells to peripheral lymphoid organs and activation (for positive selection)

36
Q

Activated B cells give rise to plasma cells and memory cells

A

antibody secretion and memory cells in bone marrow and lymphoid tissue

37
Q

Plasma cell - IgM

A

antibody secretion

38
Q

IgG Expressing B cell

A

Isotype switching

39
Q

High affinity Ig-Expressing B cell

A

Affinity Maturation
+
Memory B cell

40
Q

from naive to activated to differentitated

A
  1. Antigen recognition
    - naive (IgM, IgD) B cell + antigen
  2. Helpter T cells, other stimuli
    - Activated B cells
  3. B cell and proliferation and differentiation
    **- proliferation
  4. antibody secretion
  5. isotype switching (AID)
  6. affinity maturation (AID)
  7. memory B cell
41
Q

Memory B cell vs B plasma cell

A

Plasma cell - secretes antibodies off the surface

memory cell - antibody remains on the surface of the cell

42
Q

how does antigen get noticed by B cells

A
  • Antigen arrives from tissues via affarent lymphatics into lymphoid organs (follicle)
    1. small antigens delivered to follicles via conduits
  • May be picked up by (conventional) denritic cells in medulla and migrate to lymphoid organs (follicle)
  • Larger antigen taken up by macrophages in subscapular sinus and denritic cells in medulla and travel to follicle
43
Q

follicular dendritic cells display

A

intact antigens on their cell surface so that B cells receptors can bind to them and become activated

44
Q

enigmatic dendritic cells

A

storage vessels for antigens.

Ready for B cell stimulation.

45
Q

follicular dendritic cells express:

A

2 types of different complement receptors that bind to intact antigens or pathogens that are coated with complement opsinins.

  • CR1
  • CR2
46
Q

two types of antigens activate B cells

A
  • T dependent antigens - Require T cell help for production of antibodies
  • T independent antigens - no requirement for T cell help
47
Q

antigen binding site of the BCR

A

consists of the heavy and light chain in the variable region

48
Q

BCR signaling requires the assistance of

A

the signaling machine IgA+IgB

49
Q

B cells become activated when their receptors are cross linked by antigens

A

antigen binding site binds with high affinity to a given antigen. if that antigen is repeated on the surface of the bacteria/pathogen, then the erceptors of the B cells may express cross linkage.

Cross linkage - the receptors are brought together, so that the signal can be amplified by the fact that many B cell receptors are being triggered at the same time.

50
Q

Clustering of antigen receptors allows receptor associated kinases to phosphorylate the ITAMS

A

Syk binds to doubly phospjorylated ITAMs and is activated on binding

51
Q

Much like T cell activation, B cell activation requires cross linking (clustering) and association with signaling with signaling adapters

A

The signaling cascade is initiated from the ITAM domains in IgA, and IgB

52
Q

b cell receptors perform crosslinkage through antigens which leads to

A

change in gene expression in nucleus

53
Q

BTK

A

necessary for activation of the signaling cascade

54
Q

downstream of the signaling cascade, these trancsription factors are activated

A
  • NFAT
  • NFkB
  • AP-1

move to the nucleus where they initiate changes in gene expressions

55
Q

the signaling thorugh of BCR through IgA and IgA requires

56
Q

BCR triggering is greatly enhanced by

A
  • B cell co-receptor
  • CD40/CD40 ligand
57
Q

B cell co-receptor

A
  • CDR19/CR2/CD81 (complex)
  • increase BCR signal by up to 10,000 fold
  • work best with complement labeled antigens bringing together complement receptors and BCR
58
Q

CD40/CD40 lignad

A

Interaction with T cells
- essential for T cell help
- required for isotype switching and affinity maturation

59
Q

B- Cell complex (CR2, CD19, CD81)

A

if an antigen is bound by complement, it will bind to CR2 and then reqruit the rest of the complex to enhance signaling

B cell activation

Any complement labeled item (pathogen or protein) can bind to B cell receptor

60
Q

CD40: CD40L

A

B cells need two signals for full activation by T dependent antigens

61
Q

???????

A

B cell receptor binds an antigen. leads to signal 1 indicating B cell receotri had bound annd recognized the antigen its specific for.
Taken up bymediated endocytosis. antigen presented as MHCII

62
Q

T dependent antigens

A

require T cell help for production of antibodies
- typically protein antigens

63
Q

T independent antigens

A

TI - 1
- a combination of BCR and TLR signals activate B cell

TI-2
- Repetitive carbohydrate antigens present at high density on a pathogen surface, leads to extensive BCR cross linking

64
Q

TI - antigens require contribution from TLR signaling

A
  • B cell receptor
  • TLR4
65
Q

TI- 2 antigens

All about cross-linking

A

High density on pathogen surface
- recruit B cell receptors together
- Many repeated antigens close together

66
Q

what antibody isotype can be generated from T independent reactions?

67
Q

Differentation of activated B cells in secondayr lymphoid organs

A
  • upon antigen encounter in lymphoid organs, B cells are detained in the T cel areas where they recieve signals to proliferate and differentiate
  • some become plasma cells and migrate to medullary cords or to the bone marrow
  • plasma cells have no cell surface immunoglobin or MHC class II, no furhter division, specialized for antibody secretion
68
Q

plasma cells are devoted to

A

antibody production

69
Q

Germinal centers

A
  • Other activated B cells migrate to a nearby follicle which becomes a secondary follicle, containing a germinal center
  • these sites, are where somatic hypermutation, affinity maturation and isotype switching occurs
  • memory B cells are maintained and circulate through the body, ready to rapidly respond upon re-exposure to pathogen.
70
Q

true / false
Plasma cells undergo affinity maturation?

71
Q

B cells are prolferating and getting T cell help in this location

A

Germinal center.

  1. activation of B cells and migration into germinal center
  2. B cell proliferation
  3. Somatic mutation and affinity maturation; isotype switchong
  4. exit of high affinity antibody secreting cells and B cells
72
Q

Somatic hypermutation

A

AID makes point mutations in the variable region, leading to high affinity binding to the antigen

Immunology (18 decks)

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