Lecture 5: B Cell Development and Generation of Primary Antibody Repertoire

Question 1

Heavy chain of antibodies is encoded by ____ different gene segments as opposed to the variable region which is encoded by ___.

Answer 1

3; 2

Question 2

A single plasma cell makes ____ kind of antibody while a B cell can deviate and make 2 or more heavy chain isotypes

Answer 2

1

Question 3

What is the next stage of a B cell after stem cell?

Answer 3

ProB

Question 4

What kind of rearranging is present in ProB cells?

Answer 4

IgH DJ (no light chain rearrangements)

Question 5

What is the earliest cell type that synthesizes a detectable Ig gene product?

Answer 5

PreB cells

Question 6

What is the hallmark of the next stage, immature B cells?

Answer 6

kappa and lambda light chains that associate with mu heavy chains and the assembled IgM molecules are expressed on the cell surface

Question 7

Describe mature B cells

Answer 7

they have acquired a complete Ig and have antigen specificity so they migrate out of the bone marrow

Question 8

Mature B cells coexpress which two heavy chains?

Answer 8

mu and delta

Question 9

True or false: Mature B cells IgM and IgD each have the same V region and therefore the same antigen specificity?

Answer 9

TRUE

Question 10

Define allelic exclusion

Answer 10

the expression of only one allele in a cell

Question 11

How many varieties of V gene regions are there? D? J?

Answer 11

V: 50-100
D: 20-30
J: 5-6

Question 12

What stretches of DNA mediate VDJ recombination?

Answer 12

recognition sequences (RSS) - stretch of 7-8 nucleotides flanking D and on 3’ end of V and 5’ end of J

Question 13

What enzymes recognize RSS?

Answer 13

RAG1 and RAG2 (recognize two RSS and cleave DNA between exon and RSS)

Question 14

What is the name of the excised portion of VDJ rearrangements?

Answer 14

BREC

Question 15

How is the secreted vs. membrane IgM produced?

Answer 15

alternative splicing

Question 16

How do B cells express both mu and delta heavy chains?

Answer 16

alternative splicing of C region (same VDJs though)

Question 17

What is N-region addition and how does it contribute to antibody diversity?

Answer 17

the addition of new nucleotides to the VDJ genes during rearrangement (accomplished by deoxyribonucleotide transferase)

Question 18

What is B cell tolerance?

Answer 18

selection and removal of B lineage cells in the bone marrow that have non-functional VDJ rearrangements of express self-reactive antibody

Question 19

What are the 3 routes of removal for antibodies with self reactivity?

Answer 19

1) become anergic
2) deleted
3) rescued by receptor editing

Question 20

When is the V gene selected in recombination?

Answer 20

as a late ProB cell

Question 21

When is heavy chain rearrangement turned off?

Answer 21

when IgM goes to the surface of the cell (mu heavy chain binds to surrogate light chain that takes the molecule to the surface)

Question 22

What are 3 features that lead to a large antibody repertoire?

Answer 22

1) combinatorial V(D)J gene joining
2) N nucleotide addition by TdT
3) Combinatorial association of H and L chains

Question 23

What are TCRs?

Answer 23

T Cell Antigen Receptors (structurally similar to Ig in that they have analogous variable and constant regions)

Question 24

What are the majority of TCRs?

Answer 24

ab

Question 25

The V regions of alpha and gamma chains are encoded by ___ and ____ gene segments

Answer 25

V and J

Question 26

True or false: TCR genes rearrange by the same mechanism as Ig genes

Answer 26

TRUE

Question 27

True or false: each T cell expresses a single TCR specific for one particular antigenic determinant?

Answer 27

TRUE

Question 28

What 3 gene families encode IgG?

Answer 28

1) heavy chain
2) kappa
3) lambda

Question 29

What is a myeloma?

Answer 29

1 B cell becoming cancerous

Question 30

True or False: in pre-B cells, both heavy and light chain genes are rearranged

Answer 30

FALSE; light chains are still in their germline state - do not rearrange until immature B cell

Question 31

How does allelic exclusion work?

Answer 31

VDJh rearrangement on one allele; VJ(L) rearrangement on the other allele