B cell development

Question 1

V region exons

Answer 1

300 bp sections at the 5’ end of each Ig locus that are separated by non-coding DNA

Question 2

Joining segments

Answer 2

Downstream of the V region, they have additional coding sequences that are about 30-50 bp long

Question 3

Diversity segments

Answer 3

Additional coding sequences present downstream of V and J regions, but ONLY IN HEAVY CHAINS

Question 4

Location of C region genes

Answer 4

Varying distances in the 3’ direction from the V genes

Question 5

How many exons are in the Ch region?

Answer 5

Three to four, plus another one for either the cytoplasmic/transmembrane domain

Question 6

Ig genes are only expressed where?

Answer 6

In B cells

Question 7

Heavy chain: DJ

Answer 7

The first Ig gene rearrangement occurs here; joins one D and one J segment and deletes intervening DNA

Question 8

Heavy chain: VDJ

Answer 8

After DJ rearrangement, one of the many V genes is attached to the DJ complex. All segments 5’ to the DJ complex are deleted

Question 9

What is significant about the VDJ rearrangement step?

Answer 9

Only happens in cells committed to be B cells, and it is a highly regulated step because V transcription begins right after deletion of the unused D segment

Question 10

Light chain: VJ

Answer 10

VJ complex is formed in the light chain after complete VDJ rearrangement of the heavy chain.

Question 11

When does transcription begin for the light chain?

Answer 11

When the C region is joined to the VJ complex

Question 12

Formation of immature B cell

Answer 12

The kappa chain completed after light chain rearrangement joins with mu segment from heavy chain rearrangment, making IgM, which is then expressed on the cell surface

Question 13

Major rule of antibody production

Answer 13

One B cell makes only one kind of antibody because of allelic exclusion

Question 14

How does the B cell bypass the major rule of antibody production?

Answer 14

Alternative splicing after mRNA production

Question 15

ProB cells

Answer 15

Precursor of PreB cells; have heavy chain DJ rearrangements and no light chain rearrangements

Question 16

PreB cell

Answer 16

Earliest cell that produces mu heavy chain with variable and constant domains; only found in hematopoietic tissues.

Question 17

What comprises a preB receptor?

Answer 17

Mu chains, surrogate light chains, Ig-alpha and Ig-beta

Question 18

Immature B cell

Answer 18

Kappa or lambda light chains are now produced, associating with the previously made mu chains and expressing IgM on the surface
Cannot respond to antigens

Question 19

Mature B cell

Answer 19

Complete Ig; migrate out into the periphery and can respond to antigens

Question 20

How do B cell IgM and IgD respond to the same antigens?

Answer 20

They both have the same V region and therefore the same antigen specificity

Question 21

Recognition sequences

Answer 21

DNA sequence that mediates the recombination of V, D, and J gene segments; located on either side of the D segments and after V or before J

Question 22

RAG1 and RAG2

Answer 22

Recognize RSSes, loop them together, and excise them out, leaving just the exons that are joined by DNA ligase

Question 23

Are all rearrangements functional?

Answer 23

No

Question 24

BRECs

Answer 24

The excision loops that are left behind after RAG1/RAG2 activity. Clinically important for testing B cell proliferation after bone marrow transplants

Question 25

TdT

Answer 25

Mediates random addition of new nucleotides added to the junctions during VDJ rearrangement

Question 26

Junctional diversity by N-region addition

Answer 26

N sequences are added into the junctions during VDJ arrangement

Question 27

What happens to B cells that have nonfunctioning VDJ?

Answer 27

They are deleted

Question 28

What happens when B cells have anti-self reactivity?

Answer 28

Can become anergic, can be deleted, or can try and be salvaged by receptor editing

Question 29

Receptor editing

Answer 29

When anti-self is detected, B cell maturation arrests and new combination is used. If that new specificity also is self-reactive, the cell is killed. If not, it can continue as a functional B cell

Question 30

Most T cells have what type of receptors?

Answer 30

Alpha/beta receptors (5% have delta-gamma)

Question 31

Functional structure of a T cell receptor

Answer 31

Has two alpha and two beta domains, variable domains on the periphery