Subtopic: Fundamentals of Downstream processing (chromatography, filtration)
Question Statement:
For monoclonal antibody production, hypoxanthine ____________.
Options:
(A) allows DNA synthesis in the absence of de novo dTMP synthesis
(B) allows purine synthesis in cells containing HGPRT
(C) induces cell fusion
(D) prevents de novo nucleotide synthesis
Official Answer Key:
B
Step-by-Step Solution & Explanation
### **Official Solution & Concept Analysis (GATE BT 2026 Q.18)**
**1. Governing Concept**:
- **Topic**: Immunology & Hybridoma Technology (HAT Medium Selection)
- In the Köhler and Milstein hybridoma technique, myeloma cells (lacking HGPRT, $\text{HGPRT}^-$) are fused with antibody-producing B lymphocytes ($\text{HGPRT}^+$):
- In **HAT medium** (Hypoxanthine, Aminopterin, Thymidine):
- **Aminopterin** blocks the *de novo* purine and pyrimidine synthesis pathways by inhibiting dihydrofolate reductase.
- Cells are forced to survive via the **salvage pathway**:
- **Hypoxanthine** provides the purine salvage substrate, converted to IMP by **HGPRT** (Hypoxanthine-Guanine Phosphoribosyltransferase).
- **Thymidine** provides the pyrimidine salvage substrate, converted to dTMP by Thymidine Kinase (TK).
- Unfused myeloma cells die because they lack HGPRT and cannot utilize hypoxanthine. Only hybridomas (which inherit HGPRT from the B cell) survive.
**2. Option Analysis**:
- **Option (A) is INCORRECT**: Hypoxanthine does not inhibit aminopterin; it is the salvage substrate.
- **Option (B) is CORRECT**: Serves as a vital purine precursor for nucleotide synthesis via the HGPRT-catalyzed salvage pathway when the *de novo* pathway is blocked.
- **Option (C) is INCORRECT**: Hypoxanthine is a purine, not a pyrimidine precursor (thymidine serves as pyrimidine precursor).
- **Option (D) is INCORRECT**: Hypoxanthine does not induce membrane cell fusion (PEG or electrofusion does).
**3. Final Answer**:
- **Correct Choice**: **B**
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