Lesson 5 of 5 / Immune recognition and memory
Recombination, hypermutation and class switching
Which process changes binding specificity, and which changes the kind of help recruited?
In this lesson: Explain how antibody diversity and specialised functions arise.
About 8 min
The key ideaV(D)J assembly builds binding-site diversity; hypermutation and selection refine affinity; class switching changes the heavy-chain constant region.
From recognition to response
Which region changes during each process?
V1-D2-J1 is one arrangement. Heavy chains combine V, D and J; light chains combine V and J. Segment choices, junction variation and heavy/light pairing generate diversity. The small number of boxes is illustrative, not a count of all human segments.
Explanation
During B-cell development, variable-region genes are assembled from gene segments by somatic recombination. Heavy chains combine V, D and J segments; light chains combine V and J. Alternative segment choices, variation at joins and pairing of different heavy and light chains generate a very large repertoire before a particular antigen is encountered.
After activation, somatic hypermutation introduces changes into immunoglobulin variable-region sequences in proliferating B cells. Variants differ in affinity; cells that bind and obtain appropriate help more effectively can be selected. Repeated mutation and selection can increase average affinity, called affinity maturation. The mutations are not guaranteed individually to improve binding.
Class switching changes the heavy-chain constant-region sequence used, for example changing an IgM response to an IgG response. The assembled variable region is retained, so class switching itself generally preserves antigen-binding specificity while changing effector properties and distribution.
These processes should not be collapsed into one explanation. Recombination creates combinations, hypermutation can alter variable-region affinity, and class switching supplies different constant-region functions. They occur in somatic immune cells and are not a process by which acquired antibody genes are normally passed to a person's children through gametes.
Step by step
- 1
Identify the region changed
Variable-region assembly or constant-region switching?
- 2
Place the event in time
Initial repertoire versus antigen-driven maturation.
- 3
State the consequence precisely
Specificity/affinity and effector class are different properties.
Worked example
Work through the evidence
A B-cell lineage changes from IgM to IgG while retaining its assembled variable-region sequence. Must it now bind a different antigen?
One way to explain it
No. Class switching changes the heavy-chain constant region and effector properties while retaining the variable-region specificity, apart from any separate hypermutation events.
Why this answer works
- Separate switching from concurrent affinity maturation.
- The same binding specificity can be deployed in different antibody classes.
Is this true? "Class switching creates a completely new antigen-binding site by replacing the variable region."
It changes the heavy-chain constant region; variable-region changes belong to other diversification processes.