Which enzyme rearranges immunoglobulin gene segments in developing B cells to generate diverse antibodies?

• A. RAG-1 and RAG-2
• B. TdT
• C. AID
• D. DNA ligase IV

Answer: (A)

V(D)J recombination in developing B cells is driven by the RAG complex. RAG-1 and RAG-2 recognize recombination signal sequences flanking the V, D, and J gene segments and introduce precise double-strand breaks. This creates new coding regions by rearranging the segments that will encode the antibody heavy and light chains. The broken ends are then processed and joined by the nonhomologous end joining machinery, generating diverse variable regions.

Nucleotide additions at the junctions, increasing diversity, are introduced by TdT during this process, but TdT itself does not rearrange the gene segments. Activation-induced cytidine deaminase (AID) acts later in mature B cells to drive somatic hypermutation and class switch recombination, not the initial rearrangement. DNA ligase IV is involved in sealing the DNA ends during the joining step, not in initiating the rearrangement.