Question

Consider a hypothetical chromosome in which heavy chain constant genes occur in the following order: μ, δ, α, γ2, γ1, γ4 and ε.

A. Name the process in whese these different constant genes are sequentially expressed.

B. Which of the following if any, is/are possible sequential outcomes

1. express μ and δ then γ1 then γ4 and ε or 2. express μ and δ then  γ2 then γ1

or 3. express μ and δ then α then ε or 4. express μ and δ then γ2 then γ1 and α or 5.

express μ and δ then γ3 or 6. express μ and δ then μ

C. In what environment does this occur;?

D. List the cell interactions required to drive this process?

Answer 1

A. The process in which these different constant genes are sequentially expressed is known as class switching since there is a shift from one class of immunoglobulins to another class depending on the requirements of the B-cells.

B. The sequential order of heavy chain constant genes according to the question is as follows :

п, о, а, 2, 1, 4, є

The possible sequential outcomes are as follows :

1.  express μ and δ then γ1 then γ4 and ε

2. express μ and δ then  γ2 then γ1

3. express μ and δ then α then ε

The other outcomes are not possible since class switching occurs through recombination between switch regions (S) of each heavy chain gene segment. This recombination results in deletion of all gene segments between the recombining gene segments. Thus once a class switch has been made , it becomes impossible to express any CH gene segment that used to reside between μ and the new gene segment.

3. Mature B-cells express both mIgM and mIgD. The decision to translate μ and δ heavy chains is made at the level of RNA splicing. A B-lymphocyte generally produces only a single class of Immunoglobulin at any one time, but the class may change during the cell lineage. Class switching occurs in antigen-stimulated mature B-cells synthesizing IgM and IgD.

4. Cytokines released by T-cells induce class switching . In addition. membrane interactions between CD40 on the B-cell and CD40L on TH cell aid in class switching where TH cell presents the antigen to the B-cell causing B-cell activation and production of immunoglobulins accordingly.