Immunoglobulin Genes

Question 1

How diversity in antibodies is created at the gene level

Answer 1

Gene rearrangement: many different fragments exist on germline cells, but B cells have only one fragment from each component

Question 2

Fragments involved in antibody light chains

Answer 2

V (variable), J (joining), C (constant)

Question 3

Fragments involved in antibody heavy chains

Answer 3

V (variable), J (joining), D (diversity), C (constant)

Question 4

Chromosomal location of antibody genes

Answer 4

2 parts of Ig that come together (light and heavy chains) are coded for on different chromosomes
2 types of light chains (lambda and kappa) are coded for on different chromosomes
3 chromosomes total involved

Question 5

Gene rearrangement process for light chain vs heavy chain

Answer 5

Light chain: one recombination event (V-J joining)

Heavy chain: two recombination events (D-J joining, V-DJ joining)

Question 6

Site of DNA cleavage

Answer 6

Recombination signal sequence

Question 7

Order of heavy chain gene recombination

Answer 7

Rearrangement of one allele
If unsuccessful, rearrangement of second allele
If unsuccessful, cell death
If rearrangement is successful, stimulation of light chain rearrangment

Question 8

Allelic exclusion

Answer 8

Only one Ig allele is expressed in the antibody (true for both heavy and light chains)

Question 9

Order of light chain gene recombination

Answer 9

Rearrangment of one kappa allele
If unsuccessful, rearrangement of second kappa allele
If unsuccessful, rearrangement of lambda allele
If unsuccessful, rearrangement of second lambda allele
If unsuccessful, cell death

Question 10

Isotypic exclusion

Answer 10

In one B cell, there will be either a lambda or a kappa chain, not both

Question 11

Isotype switching occurs where?

Answer 11

Mature B cell, exposed to antigen

Question 12

Is isotype switching a reversible process?

Answer 12

No- the looped out DNA is gone

Question 13

Isotype switching purpose and mechanism

Answer 13

Purpose: letting B cell produce other types of Igs other than IgM
DNA strand contains all isotypes of Ig- IgM is first in order
DNA loops out isotypes proceeding desired isotype (ex- loops out IgM and IgD so that IgG can be produced)

Question 14

Membrane-bound vs secreted Ig: how produced

Answer 14

RNA splicing of Ig transcript removes exon that codes for membrane-bound portion of Ig to create secreted Ig

Question 15

What enables co-expression of IgM and IgD?

Answer 15

Alternative RNA processing: polyadenylation and splicing

Question 16

Where Ig is synthesized in cell

Answer 16

Rough endoplasmic reticulum

Question 17

3 types of DNA regulatory sequences that regulate transcription of Ig genes

Answer 17

Promoters: initiate transcription
Enhancers: help transcription to occur
Silencers: block transcription

Question 18

5 ways that diversity of Ig genes is generated

Answer 18

1. Gene rearrangement (VDJ pairs)
2. Combinatorial association of heavy and light chains
3. Somatic hypermutation
4. Alternative splicing
5. Base insertion (addition of a few bases at splice site)

Question 19

Somatic hypermutation is unique to what kind of cells?

Answer 19

B cells

Question 20

Somatic hypermutation: what it does and how it works

Answer 20

Increases diversity of variable regions of Igs

Mutation in variable regions following antigen exposure leading to increased antigen binding strength