Generation of antibody diversity

Question 1

How is antibody diversity reached:

Answer 1

Array of different antigen specificity is achieved by recombination of antibody genes during antigen independent differentiation of B-cells in bone marrow.

Question 2

What are our 3 antibody genes?

Answer 2

2 light chain (kappa and lambda) and 1 heavy chain gene

Question 3

How is the kappa-light chain gene segment organised in germline DNA?

Answer 3

Singal sequences preced each V gene segment and stop sequences follow the C-kappa gene segment.
V, J, C

Question 4

What is V

Answer 4

Variable gene segment

Question 5

What is J

Answer 5

Joining gene segment

Question 6

What is C

Answer 6

Constant gene segment

Question 7

What is D

Answer 7

Diversity gene segment

Question 8

How is the heavy chains gene segment in germline DNA organised?

Answer 8

Each CH gene segment is made of several exons.
Singal leader sequences precede each V gene degment and stop sequences follow heavy chain gene segments.
V, D, J, C

Question 9

When do Ig genes become functional?

Answer 9

When they are rearranged

Question 10

When are Ig genes rearranged?

Answer 10

During antigen independent differentiation of B cells in the bone marrow.

Question 11

What does each light chain use to generate the coding region of the variable domain?

Answer 11

One V and one J gene segment

Question 12

What does each heavy chain use to generate the coding region of the variable domain?

Answer 12

One V, one D and one J segment

Question 13

What is the process of Ig gene rearragment called?

Answer 13

V(D)J recombination

Question 14

What are the basic principles of light chain gene recombination?

Answer 14

In germline DNA: somatic recombination VJ joining
In rearranged DNA of Pre-B-cell: Transcription
RNA splicing produces mRNA in the virgin B cell

Question 15

Where is the light chain mRNA translated?

Answer 15

ER

Question 16

Where do the light chains associate with the heavy chains to make an antibody?

Answer 16

ER

Question 17

What are the basical principles of heavy chain gene recombination?

Answer 17

Germline DNA: Somatic recombination DJ joining: Then somatic recombination VDJ joining
In the rearranged DNA pre-B-cell: Transcription
Primary RNA transcript: RNA splicing
mRNA in virgin B cell

Question 18

What is junctional diversity?

Answer 18

Where nucleotides are added/removed at random sites, V, D and J gene segments are recombined.

Question 19

What does the D segment partially code for>

Answer 19

The 3rd CDR corresponding to the join between the V and J segment in the heavy chain.

Question 20

What does junctional diversity increase>

Answer 20

Number of antigenic specificities

Question 21

When do B cells switch Ig class?

Answer 21

As immune response matures.

Question 22

What Ig do naive B-cells exiting the bone marrow express?

Answer 22

IgM and IgD on their cell surface.

Question 23

What is the 1st Ig secreted in response to antigens?

Answer 23

IgM

Question 24

As the humoural response matures B-cells undergo class switching, the Igs expressed are:

Answer 24

Either IgE, IgA or IgG instead of IgM/D.

Question 25

Why is class switching useful?

Answer 25

Tailors humoral response to antigen.

Question 26

What part of the antiobdy actually switches?

Answer 26

Constant region of the heavy chain.

Question 29

Genetic basis of isotype switching: When the B-cell DNA is after VDJ recombination what Igs does it make?

Answer 29

IgM and IgD

Question 29

After isotype switching what occurs to the B-cell DNA

Answer 29

IgM and IgD heavy chain encoding regions are excised.

Question 29

Why doesn’t class switching alter the antigenic specificity of the antibody?

Answer 29

Light chain and VH domains are retained.

Question 29

In context of genes: why is the antigenic specificity unalterted during isotype switching?

Answer 29

VDJ segment is the same.