Development of B-cells Flashcards

1
Q

What are the six phases of B-cell development?

A
  1. Repertoire assembly
  2. Negative selection
  3. Positive selection
  4. Searching for infection
  5. Finding infection
  6. Attacking infection
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2
Q

The first 3 phases of B-cell development occur in ______, while the last 3 phases occur in ______.

A
  1. Bone marrow
  2. Blood vessels & lymphatics
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3
Q

Which hematopoietic cell can differentiate into a B-cell or T-cell?

A

Common lymphoid progenitor

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4
Q

Which of the following transmembrane proteins is the only one present on pluripotent hematopoietic stem cells?

  • CD10
  • CD34
  • CD127
  • CD19
A

CD34

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5
Q

True or false. When a B-cell precursor differentiates into a pro-B cell, it is no longer capable of self-renewal.

A

False. Pro-B cells are able to self-renew

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6
Q

Dh and Jh joining occurs in _____ cells

A

Early pro-B cells

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7
Q

Vh segment joins DJh segment in _____ cells

A

Late pro-B cells

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8
Q

Expression of functional μ chains occurs in _____ cells

A

Large pre-B cells

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9
Q

Light chain rearrangement and assembly with μ-chain occurs in ______ cells

A

Small pre-B cells

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10
Q

Membrane-bound IgM associates with Igα and Igβ in ______ cells

A

Immature B cells

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11
Q

Is the light chain or heavy chain more specific?

A
  • Light chain is more specific
  • If the body makes a good heavy chain, it will amplify the population of cells that can express that heavy chain so light chains can be processed from there
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12
Q

A ______ of growth factors and transcription factors drive immune cell differentiation

A

Gradient

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13
Q

___% of pre-B cells go on to become immature B-cells

A

50%

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14
Q

What is the function of stromal cells in bone marrow?

A

Make contact with maturing B cells and secrete growth factors for maturation

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15
Q

True or false. The default pathway for B-cell development is to die by apoptosis unless a survival signal is received.

A

True

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16
Q

What is the difference between productive and nonproductive rearrangement?

A
  • Productive - complete and functional Ig produced from rearranged genes
  • Nonproductive - rearrangement does not translate into a functional Ig
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17
Q

What is the consequence of not having a functional Rag gene on either chromosome?

A

No rearragement can occur to create antibodies

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18
Q

What are the two criteria requirements for a pro-B cell to survive?

A
  1. Make a μ chain
  2. μ chain must be able to bind to a light chain (surrogate chain)
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19
Q

What are the two components of the surrogate light chain and function to mediate binding to receptors on stromal cells?

A
  • VpreB
  • λ5
20
Q

How does a pro-B-cell initiate pre-B-cell receptor assembly?

A
  1. Igβ shuts down RAG gene transcription
  2. RAG proteins are degraded
  3. Chromatin Structural changes prevent gene rearrangement
21
Q

What is allelic exclusion?

A

When a cell only expression one of its two copies of a gene

22
Q

What is allelic exclusion?

A

Cell only expresses one copy of its two genes

23
Q

What is the consequence of not having allelic exclusion in B-cell receptor formation?

A

Low avidity binding

24
Q

___% of pre-B-cells have productive rearrangement

A

85%

25
Q

RAG is expressed in what stages of B cell development?

A
  • Early pro-B
  • Late pro-B
  • Large pre-B
  • Immature B
26
Q

Kit (growth factor receptor) is expressed in what stages of B-cell development?

A
  • Stem cell
  • Early pro-B
27
Q

IL-7 (growth factor receptor) is expressed in what stages of B-cell development?

A
  • Stem cell
  • Early pro-B
  • Late pro-B
  • Large pre-B
28
Q

CD25 (growth factor receptor) is expressed at what stages of B-cell development?

A
  • Late pro-B
  • Large pre-B
29
Q

RAG1 and RAG2 are expressed in what stages of B-cell development?

A
  • Early pro-B
  • Late pro-B
  • Immature B
30
Q

λ5 and VpreB are expressed in what stages of B-cell development?

A
  • Early pro-B
  • Late pro-B
  • Large pre-B
  • Small pre-B
31
Q

Of the two B-cell populations (B1 and B2), what is the difference between their modes of renewal?

A
  • B1: self-renewing
  • B2: replaced from bone marrow
32
Q

B1 cells make up approximately ___% of B-cells

A
  • ~5%
  • Less diverse than B2
33
Q

Why do B1 cells have a lower affinity for their antigens than B2 cells?

A
  • Polyspecific
  • Recognize bacterial polysaccharides, not proteins
34
Q

Where are B-cells typically found?

A
  • Blood
  • Lymph
  • Secondary lymphoid organs
  • Bone marrow
35
Q

____% of immature B-cells bind self-antigen

A

75%

36
Q

In what stage of B cell development does negative selection occur?

A

Immature B-cells

37
Q

What are the two potential fates of an immature B cell during negative selection?

A
  • If it doesn’t recognize self-antigen, it ends the blood and expresses IgD and IgM
  • If it does recognize self-antigen, it is retained in the bone marrow and given a second chance to rearrange light chain
38
Q

_____ is a state of nonresponsiveness to an antigen

A

Anergy

39
Q

What is the life span of an anergic B-cell vs. a normal B-cell?

A
  • Anergic: ~1-5 days
  • Normal: ~40 days
40
Q

What are the possible fates for self-reactive B-cells in the bone marrow (central tolerance)?

A
  • Receptor editing
  • Apoptosis
  • Anergy
41
Q

What are the possible fates for self-reactive B-cells in the periphery? (Peripheral tolerance).

A
  • Apoptosis
  • Anergy
42
Q

What is the function of high endothelial venules (HEV) in secondary lymph organs?

A

Delivery of B-cells (mature and immature) to lymph nodes in search of their corresponding antigens.

43
Q

What is the function of chemokines?

A

Attracts B-cells

44
Q

What chemokine is expressed in lymph node cortices and dendritic cells in lymph nodes?

A

CCL21

45
Q

What chemokine is expressed solely on B-cells?

A

CCR7

46
Q

What chemokine is expressed by dendritic cells in lymph nodes to attract B cells?

A

CCL19

47
Q

______ are specialized stromal cells not of hematopoietic origin that secrete CXCL13 to attract B-cells to the primary follicle for maturation.

A

Follicular dendritic cells (FDCs)