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Microbiology · Immunology: affinity maturation
Sample itemOver successive tetanus toxoid boosters, a child's antibodies bind the toxin with progressively higher affinity, and sequencing of antibody genes from B cells shows many point mutations in the variable regions. Which enzyme is responsible and where does the process occur?
Original practice item, not a recalled exam question. Nothing here is recorded.
The answer and the reasoning
C. Activation-induced cytidine deaminase in germinal centres
Antigen-activated B cells in germinal centres undergo somatic hypermutation of variable region genes through activation-induced cytidine deaminase. Follicular dendritic cells and T follicular helper cells then select clones with higher affinity, which is affinity maturation. The same enzyme drives class switch recombination.
Option by option
A. Terminal deoxynucleotidyl transferase in thymic medulla
Terminal deoxynucleotidyl transferase adds nucleotides at junctions during early receptor assembly, not after antigen contact.
B. RAG1 and RAG2 recombinases in bone marrow pro-B cells
RAG recombinases perform antigen-independent V(D)J recombination in the bone marrow and do not cause point mutations after antigen exposure.
C. Activation-induced cytidine deaminase in germinal centres (correct)
Correct. This deaminase introduces point mutations in V genes of germinal centre B cells, and selection gives higher affinity.
D. Perforin in the lymph node paracortex
Perforin is a cytotoxic granule protein that forms pores in target cells and does not mutate immunoglobulin genes.
Source note: Original NextPrep sample item — pending expert review. This item is original practice material awaiting independent expert review, so confirm important facts in a standard textbook.
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