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Immunology > B Cell Development > Flashcards

B Cell Development Flashcards

1
Q

What is required for the generation of antibodies?

A

Ig gene rearrangements

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2
Q

What antibodies are made in the B Cells?

A

IgM

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3
Q

What is the gene rearrangement process for the light chain?

A

The germ line DNA has the V gene rearrange with the J gene into a VJ gene. Then the genes between them are deleted. This forms the LVJ necessary for the expression of the light chain.

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4
Q

What is the gene rearrangement process for the heavy chain?

A

The germ line DNA has the D and J rearrangement as the first to occur. Then a V and DJ rearrangement occurs and leads to the VDJ formation which is necessary for the heavy chain.

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5
Q

Is Ab synthesis antigen driven?

A

No. The process occurs entirely independently and does so at random.

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6
Q

For the heavy chain rearrangement, are there residual V genes?

A

Yes, upstream

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7
Q

For the heavy chain rearrangement, are there residual D genes?

A

No, both upstream and downstream D genes will all be deleted

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8
Q

For the heavy chain rearrangement, are there residual J genes?

A

Yes, downstream

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9
Q

What are the steps in B cell development?

A

ProB -> PreB -> Immature B -> Mature B cells

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10
Q

What is allelic exclusion?

A

Only one Vh and Vl is rearranged per B cell

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11
Q

What process is occurring during the Pro B cell stage?

A

D-J and V-DJ rearrangement of the heavy chain

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12
Q

What occurs on the surface in the Pre B cell stage?

A

Heavy chain binds to a surrogate light chain (as the true light chain rearrangement has not yet occurred) which takes it to the surface and gets a signal to turn off heavy chain rearrangement

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13
Q

What else is occurring intracellularly in the Pre B cell stage?

A

V-J rearrangement of the light chain

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14
Q

What occurs in an immature B cell?

A

VJ rearrangement of the light chain is complete and so complete IgM can be expressed on the cell surface

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15
Q

What occurs in mature B cells?

A

They have gained antigen specificity and as a result, they can express IgM and IgD on the cell surface via alternative splicing

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16
Q

What heavy chain is made by B cells?

A

Mu heavy chain

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17
Q

What mediates the V, D and J recombination?

A

The RSS (recombination signal sequence) are highly conserved stretches of seven or nine nucleotides separated by non-conserved 12 or 23 nucleotide spacers.

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18
Q

What recognizes the RSS and cleaves it?

A

RAG1 and RAG2

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19
Q

What are BRECs and why are they important?

A

B cell Recombination Excision Circles. They are important because they can be used in marrow transplant patients in order to determine whether or not transplants have been accepted.

20
Q

How are secreted and membrane IgM generated with the same VDJ region?

A

Alternative mRNA splicing

21
Q

How are IgM and IgD generated from the same B cell?

A

Alternative mRNA splicing

22
Q

Where does the difference in the secreted and membrane IgM lie?

A

Difference in secreted and membrane antibodies lies in the C region of the gene

23
Q

What mediates the V/D/J rearrangements?

A

RSS and the RAG1 and RAG2 enzymes

24
Q

What mediates the isotope switch rearrangements?

A

Mediated by switch regions and

AID (activation induced cytidine deaminase)

25
Q

What are the factors that contribute to the diversity of the antibodies?

A
  1. Combinatorial V(D)J gene joining
  2. Combination of the Vh and Vl chains
  3. N nucleotide addition by TdT
  4. Somatic hypermutation
26
Q

What is somatic hypermutation?

A

It occurs after the cells leave the bone marrow and the cells divide, there is a massive increase in the rate of mutation in order to adapt to any possible antigen.

27
Q

What is N nucleotide addition?

A

TdT enzyme steps in after excision and randomly
adds nucleotides to broken V and J ends after the BREC leaves and before they are ligated. The number and what is added is entirely random and this allows for the generation of entirely new DNA as a result.

28
Q

What enzyme is responsible to N nucleotide addition?

A

Terminal deoxynucleotidyl Transferase (TdT)

29
Q

What happens when the V(D)J rearrangements are non-functional?

A

The cells will die

30
Q

What is the most extreme outcome if an Ab is found to be self reactive?

A

They will get an apoptotic signal in the bone marrow and be destroyed

31
Q

Besides apoptosis, what else may happen to self reactive antibodies?

A

Self reactive Ab that reach the periphery will become
anergic and they do not react to antigens which
are self

32
Q

What is a process that can fix self reactive antibodies?

A

Receptor editing

33
Q

How does receptor editing work?

A

Anti-self B cells can undergo receptor editing which occurs with the up regulation of the protein RAG, leading to more rearrangements and the generation of a new B cell. If the new B cell is no longer self reactive, it can migrate to the periphery and become a mature B cell.

34
Q

Can receptor editing occur in the light chain?

A

Yes, there are V genes upstream and J genes downstream available for further rearrangement

35
Q

Can receptor editing occur in the heavy chain?

A

No. There are no further D genes available for rearrangement.

36
Q

What is the TCR and what is it similar to?

A

T cell receptor. It is similar to the Fab of the Ab on the B cells

37
Q

Where are T cells made?

A

In the thymus

38
Q

What rearrangement occurs on the alpha chain of TCR?

A

VJ

39
Q

What rearrangement occurs on the beta chain of the TCR?

A

VDJ

40
Q

What is the mediator of the TCR rearrangement?

A

RSS and RAG is the enzyme

41
Q

What are the excised loops of DNA from TCR rearrangement called?

A

T cell Rearrangement Excision Circles (TRECs)

42
Q

Do T cells undergo somatic hypermutation?

A

No

43
Q

How are the G, E and A Ab generated?

A

Isotype class switch rearrangement

44
Q

What is the switch region?

A

Where DNA switching occurs

45
Q

Where does the isotope class switch mutation occur?

A

Outside of the bone marrow

Immunology (25 decks)

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