Antibody Diversity

Question 1

What is the clonal selection hypothesis?

Answer 1

Lymphocytes express antigen receptors before encountering antigens and antigens select and activate specific lymphocytes to proliferate

Question 2

What triggers B cell activation?

Answer 2

Antigen binding to immunoglobulin receptors IgM or IgD on the B cell surface

Question 3

What is somatic recombination?

Answer 3

The rearrangement of immunoglobulin gene segments to generate diverse antibodies with unique specificities

Question 4

Where does somatic recombination occur?

Answer 4

In the bone marrow and it is antigen-independent

Question 5

What segments are involved in heavy chain recombination?

Answer 5

V variable D diversity J joining and C constant segments

Question 6

What segments are involved in light chain recombination?

Answer 6

V variable J joining and C constant segments

Question 7

What is the first step in somatic recombination for heavy chains?

Answer 7

D and J segments are joined first followed by joining of the V segment to the D-J complex

Question 8

What is the 12/23 rule in recombination?

Answer 8

Gene segments can only join if one has a 12-bp spacer and the other has a 23-bp spacer

Question 9

What enzymes control somatic recombination?

Answer 9

Recombinase-activating genes RAG1 and RAG2 and DNA repair enzymes

Question 10

How does RAG recognize gene segments for recombination?

Answer 10

By binding to recombination signal sequences RSS near the V D and J segments

Question 11

What happens after RAG enzymes cut the DNA?

Answer 11

The cut DNA forms a hairpin loop which is cleaved and processed by other enzymes to add/remove nucleotides (which introduces more diversity) and join segments

Question 12

What is the result of successful somatic recombination?

Answer 12

A functional variable region gene for an antibody, heavy / light chain is formed

Question 13

What happens if RAG proteins are defective?

Answer 13

Partial defects cause Omenn syndrome while complete absence results in Severe Combined Immunodeficiency SCID

Question 14

What is junctional diversity?

Answer 14

Diversity created by imprecise cutting during recombination adding or losing nucleotides at joining sites

Question 15

What is the role of TdT terminal deoxynucleotidyl transferase?

Answer 15

Adds random nucleotides to DNA during heavy chain recombination increasing diversity

Question 16

What is the cost of junctional diversity?

Answer 16

Imprecise joining can create non-functional sequences leading to B cell apoptosis

Question 17

How are non-functional antibody genes handled?

Answer 17

Frame shifts or non-productive rearrangements result in apoptosis of the B cell

Question 18

What is the role of recombination signal sequences RSS in recombination?

Answer 18

They guide RAG enzymes to ensure proper V D and J segment joining

Question 19

What happens after the heavy chain successfully rearranges?

Answer 19

The light chain undergoes recombination starting with kappa and if needed lambda chains

Question 20

How do B cells express antibodies on their surface and what happens to non functional antibody B cells?

Answer 20

The rearranged heavy and light chains are expressed as IgM on the cell surface and non-functional combinations lead to apoptosis

Question 21

What is RNA splicing in B cells?

Answer 21

A process that occurs at the RNA level which splices antibody RNA which enables the expression of IgD (with IgM) with the same antibody specificity as the original IgM on the surface of naïve B cells

Question 22

What are the components of the antigen-binding site in antibodies?

Answer 22

Formed by the variable regions of the heavy and light chains

Question 23

How does somatic recombination follow an ordered process?

Answer 23

Heavy chains rearrange first followed by kappa or lambda light chains

Question 24

What is apoptosis in the context of antibody diversity?

Answer 24

Self-reactive or non-functional B cells undergo programmed cell death to prevent autoimmunity

Question 25

How do heavy and light chain recombinations differ?

Answer 25

Heavy chains involve V D and J segments while light chains only use V and J segments

Question 26

What is the significance of the DNA repair process in recombination?

Answer 26

Ensures proper joining of V D J segments and contributes to diversity through junctional modifications