Question

How many recombination events are likely to occur in forming the heavy chain with the recombined locus as 5'-V17-D2-J2-C\(\mu\)-C\(\gamma\)1--C\(\epsilon\)-3' by an antigen-stimulated naïve B cell producing IgG1 antibody?

• A. One
• B. Two
• C. Three
• D. Four

Hint:

Heavy Chain Recombination: 1. $D\rightarrow J$ joining $+$ 2. $V\rightarrow DJ$ joining $+$ 3. Class Switch Recombination ($C\mu \rightarrow C\gamma_1$) = 3 Recombinations.

Answer 1

The Correct Option is C

Step 1: Understanding the Concept:
Immunoglobulin heavy chain gene assembly requires two sequential V(D)J somatic recombinations during B-cell development followed by class switch recombination (CSR) upon antigen activation.
Key Formula or Approach:
\[ \text{Step 1: } D_H \rightarrow J_H \quad | \quad \text{ } V_H \rightarrow D_HJ_H \quad | \quad \text{Step 2: Class Switch (CSR) from } C\mu \rightarrow C\gamma_1 \]

Step 2: Detailed Explanation:
Recombination events in immunoglobulin heavy chain locus maturation:
1. Event 1 (D-to-J Recombination): Somatic joining of $D_2$ segment to $J_2$ segment (mediated by RAG1/RAG2 recombinase in pro-B cell).
2. Event 2 (V-to-DJ Recombination): Somatic joining of $V_{17}$ gene segment to the preformed $D_2J_2$ complex, completing the variable exon ($V_{17}D_2J_2$) in pre-B cell.
3. Event 3 (Class Switch Recombination CSR): Antigen stimulation activates Activation-Induced Cytidine Deaminase (AID), catalyzing non-homologous recombination between switch regions ($S\mu$ and $S\gamma_1$) to switch heavy chain constant region expression from $C\mu$ to $C\gamma_1$.
Total distinct recombination events = 3.

Step 3: Final Answer:
Hence, three recombination events are likely to occur, matching option (C).