Reed-Sternberg cells are CD15+, CD30+, CD45−, and B-cell marker-negative despite having clonal Ig gene rearrangements. Their loss of B-cell markers is best explained by:

• A Chromosomal translocation silencing all B-cell surface markers simultaneously
• B Transdifferentiation from a T-cell precursor
• C EBV integration directly deleting the B-cell gene loci on chromosome 14
• D Crippling somatic hypermutations and downregulation of PAX5/OCT2, with EBV LMP1 rescuing cells from apoptosis ✓

Explanation

Reed-Sternberg cells derive from germinal center B cells that have acquired crippling somatic hypermutations preventing functional Ig expression, which normally triggers apoptosis. EBV LMP1 rescues these cells by mimicking CD40 signaling. Downregulation of key B-cell transcription factors (PAX5, OCT2, BOB1) silences the B-cell immunophenotype, explaining the CD20−/CD45− profile. This is not due to chromosomal deletion or T-cell origin.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.