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Immunology > Week 4: B Cell Development > Flashcards

Week 4: B Cell Development Flashcards

1
Q

What are B cells?

A

Cells that are responsible for antibody (Ig) production and derive from CLP

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2
Q

What do B cells differentiate to?

A

Plasma cells and memory B cell

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3
Q

What is the B cell involvement of adaptive immunity?

A
  1. Acquired immunity
  2. Highly specific (BCR)
  3. Can expand and contrast clones when needed
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4
Q

Where does the first 3 stages of B cell development occur?

A

Bone marrow

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5
Q

Where do immature B cells go to encounter antigens?

A

Secondary lymphoid tissues

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6
Q

What are phases of B cell activation?

A
  1. Repertoire assembly
  2. Negative selection
    3 Positive selection
  3. Searching for infection
  4. Finding infection
  5. Attacking infection
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7
Q

What makes up the dynamic and complex structure of BM?

A
  1. Hematopoetic stem cells
  2. Stromal cells
  3. Adhesion molecules
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8
Q

What are HSCs?

A

Within the bone marrow differentiate into many cell types

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9
Q

What is stromal cells?

A

In BM that provide support and growth factors to developing cells

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10
Q

What are adhesion molecules?

A

Hold progenitor cells to stromal cells so that the stromal cell can provide stimulation for development to B cell progenitor allowing interaction of stem cell factors with its receptor c-kit on progenitors

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11
Q

What are IL7?

A

Growth factor for both T and B cells
2. Signals in JAK STAT leading to the expression of B cell transcription fact Pax5

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12
Q

What is the function Pax5?

A

Shuts down the pathway to produce T and NK cells and commits the CLP to becoming a B cell

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13
Q

What does B cell activation lack?

A

NOTHC 1 signaling

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14
Q

What are CXCL12?

A

Secreted by stromal cells to progress into the pro B cell stage

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15
Q

What are BCR?

A

Glucoproteins responsible for the antigen binding diversity of B cells

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16
Q

What are the components of BCRs chains?

A
  1. Polypeptide chains - 2 identical heavy chains, 2 identical light chains
  2. Light chain is covalently liked to amino-terminal part of heavy chain by disulfide bond
  3. Stem is made of 2 carboxyl-terminal portions of heavy chains linked by disulfide
  4. Glycol portion is attracted to the heavy chains
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17
Q

What is the function of BCR variable region?

A

Provides the diversity of BCR/Ig/ antibodies

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18
Q

Describe the components of antigen binding site of BCR?

A
  1. 1 heavy and 1 light chains
  2. Each Y shapes BCR/antibody has 2 identical antigen binding sites
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19
Q

What is the constant region of the BCR?

A
  1. Mediate the biological activities of BCR when secreted from the B cell
  2. Limited variation in aa sequence between BCR/antibodies
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20
Q

What are found on each V domain?

A

2 hypervariabl regions (HV)

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21
Q

What forms the antigen binding site?

A

The paining of heavy and light chain in the variable region brings together HV regions

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22
Q

Why is HV regions different?

A

Creates the specificity and diversity of the antigen binding sites

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23
Q

What complementary determine regions?

A

3 HV loops (CDR1, 2, and 3) that provide a binding surface complementary to the antigen

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24
Q

What occurs during the Pro-B cell stage?

A
  1. Earliest stage
  2. Maintains a limited capacity of cell renewal
  3. Ig heavy chain gene rearrangement (chromosome 14)
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25
Q

What occurs during the 2 substages of pro-b stage?

A
  1. Early: Dh to Jh rearrangement occurs
  2. Late: Vh to DJh rearrangement occurs
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26
Q

When would BCR gene rearrangement occurs?

A
  1. Prior to antigen exposure
  2. Generates the vast diversity of antigen binding region of BCR/Ig
27
Q

What is gremlin?

A
  1. Predecessor of BCR/Ig genes
  2. The heavy chain gene cluster is located on chromosome 14 in humans.
  3. It encodes the IgM (m) heavy chain on naïve B cells.
28
Q

What are the types of light chains?

A
  1. Genes encoding kappa light chains are located on chromosome 2
    2, Genes encoding lambda light chains are located on chromosome 22
29
Q

Where is BCR assembled?

A

Er and Golgi then transported to the surface of the B cell

30
Q

What does an Ig gene do to be expressed?

A

Individual gene segments must first be rearranged to assemble a functional gene that will be transcribed into mRNA and translated into protein.

31
Q

What are the genes that encode Ig polypeptides?

A

k, lamda, and H chain families

32
Q

How are k and lamda similar?l

A

contain constant (C), variable (V), and joining (J) gene segments.

33
Q

What are the components of H chain locus?

A

VH and JH segments, a group of diversity (DH) segments, and 9 CH segments.

34
Q

What are Ch segments?

A

segments correspond to the 9 classes and subclasses of human H chains

35
Q

Describe the process of somatic recombination of the heavy chain?

A
  1. The gene rearrangement at the H chain is slightly different.
  2. D joins with J segment (D-J joining)
  3. V region is joined to the DJ segment by a second recombination to form VDJ segment.
  4. VDJ is then joined to Cm and Cd segments
  5. This rearranged DNA undergoes transcription and translation to produce an Ig H chain.
36
Q

What is nonproductive rearrangement?

A

the proper reading frame is NOT preserved (results in premature stop codons) or otherwise fails to give rise to a functional Ig protein.

37
Q

What is productive Ig heavy chain rearrangement?

A

Translated into a protein called cytoplasmic  (c) that goes to the cell surface as a part of the Pre-B Cell Receptor

38
Q

What happens when a B cell expresses a µ chain?

A

Becomes a pre-B cell

39
Q

What are the stages of pre-B

A

Large and small

40
Q

What occurs during large pre-b stage?

A
  1. cells under go 5-6 rounds of rapid cell division,
  2. Have successfully rearranged a heavy chain gene but have not rearranged their light chains
41
Q

What occurs during small pre-B stage?

A
  1. non-dividing pre-B cells that are undergoing Ig light (Ig L) chain rearrangement. (VL to JL rearrangement)
  2. If the light chain rearrangement fails to produce a variable k chain then the l light chains are rearranged
  3. Light chain proteins and m heavy chains are assemble in the ER to form membrane bound IgM.
  4. IgM then associates with Ig and Igb to form a functional BCR that is transported to the cell surface
42
Q

What occurs during the somatic recombination of the light chain?

A
  1. rearranges the order of the various segments within the L chain loci to create a functional Ig gene.
  2. Recombination generates diversity within the V regions of the L chain polypeptides.
  3. Brings 1 V, J, and C segment close together
    The rearranged segment undergoes transcription and translation to produce the new light chain.
  4. The recombination at the k or l loci occurs primarily in the BM independent of antigen exposure.
43
Q

What occurs during Pre-BCR assembly signaling?

A
  1. Allelic exclusion
  2. Promotion of survival and further differentiation
44
Q

What occurs during allelic exclusion?

A
  1. Ig H chain rearrangement stops
  2. Only one Ig H chain allele (m chain) is expressed
  3. Expresses only 1 out of 2 copies of the H gene
  4. Results in B cells with a single antigen specificity
45
Q

What are the components of pre-BCR?

A
  1. µ heavy cahin
  2. surrogate light chains: two invariant proteins that mimic the Ig light chain
    3) Iga and Igß –the signal transduction molecules
46
Q

Describe the rearrangement of hIgL chain genes that lead to cell0surface IgM?

A
  1. Having 2 light chain isotypes increases the chances that the pre-B cell will produce a functioning BCR.
  2. Once IgM is on the cell surface, this signals the shut off the gene rearrangement.
  3. Now the pre-B cell differentiates into a immature B cell.
47
Q

What is the function of Iga and Igß?

A
  1. Send a signal when the BCR binds antigen. This is mediated through an ITAM domain (immuno-receptor tyrosine-based activation motif) in the cytoplasmic tail of the molecules.
  2. Whether the binding of a ligand is required for the pre-BCR to send a signal is still controversial.
48
Q

What are the checkpoints of B cells?

A

1st: is there a functional BCR
2nd Are the light chains function;

49
Q

What is the default pathways of lymphocyte development?

A

Apoptosis

50
Q

How does a lymphocyte bypass apoptosis?

A

Expression of the pre-BCR and then the BCR give survival signals

51
Q

Describe B cell negative selection?

A
  1. Mediates the removal of autoreactive B cell clones (B cells that bind self antigen)
  2. Mediated by the high affinity BCR binding of self antigens.
52
Q

What are the 3 eliminations of immature B cells that encounter self antigens?

A
  1. Clonal deletion
  2. Receptor editing
  3. Anergy
53
Q

What is clonal deletion?

A

Strongly autoreactive cells by apoptosis

54
Q

What is receptor editing?

A

Reactivation of light recombination machinery

change in the Ig specificity of an autoreactive B cell due to a rearrangement of the Ig light chain

55
Q

What is anergy?

A

Induction of non-responsiveness of further stimuli (even self-antigen stimuli)

56
Q

What is Ig specificity?

A

a change in Ig light chain can result in an Ig specificity that no longer recognizes “self” antigen and is no longer autoreactive

57
Q

What is central tolerance?

A
  1. Immunological tolerance that occurs in the primary lymphoid tissue–where lymphocytes are produced (for B cells this is BM)
  2. Removes self-reactive B cells before leaving the BM.
  3. Cells are removed by clonal deletion and receptor editing
58
Q

What is peripheral tolerance?

A
  1. immunological tolerance that occurs in the periphery, not thought to include receptor editing, (although this is controversial).
  2. Removes circulating B cells that are reactive against self antigen
59
Q

Describe the process of B cell maturation?

A
  1. Immature (transitional) B cells begin to recirculate between the blood and lymph
  2. Express high levels of IgM and low levels of IgD
  3. Maturation occurs when immature B cells enter the secondary lymphoid tissues.
  4. Chemokines draw the B cells into these tissues to the follicular region-primary lymphoid follicles
  5. B cells then interact with follicular DC’s, which drives B cell maturation through the pro-survival cytokine BAFF (B-cell Activating Factor)
  6. The B cell is now mature and is waiting to interact with antigen
60
Q

Describe recirculation of mature B cells?

A
  1. Enter secondary lymphoid tissues through specialized high endothelial venules (HEV)
  2. Pass through the primary lymphoid follicle (B cell area)
  3. Exit through the efferent lymphatic vessel if they do not encounter antigen
61
Q

What are primary lymphoid follicles?

A

organized structures of B cells enmeshed in a network of stromal cells called follicular dendritic cells with long processes that touch B cells (not hematopoietic in origin and unrelated to other DCs)

62
Q

What is the function of cytokines towards B cells?

A

Produced by stromal cells direct homing of B cells in the blood to secondary lymphoid tissues through T cell zones and into primary lymphoid follicles (B cell area).

63
Q

What happens if a B cell doesn’t encounter a specific antigen?

A

Passes through the secondary lymphoid tissue, exits through efferent lymphatic vessel, and re-enters the blood

64
Q

What are mature B cells?

A

Interact with specific antigen will undergo activation resulting in an immune response

Immunology (17 decks)

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