In X-linked agammaglobulinemia (Bruton disease), the underlying defect is mutation of BTK, a tyrosine kinase essential for which developmental step?
- A Transition from pro-B to pre-B cell in bone marrow, specifically signaling through the pre-BCR ✓
- B Isotype class switching in germinal centers
- C Thymic positive selection of CD4+ T cells
- D Terminal differentiation of pre-B cells to plasma cells
Correct answer: A. Transition from pro-B to pre-B cell in bone marrow, specifically signaling through the pre-BCR
Explanation
BTK (Bruton tyrosine kinase) is required for signaling through the pre-B cell receptor (pre-BCR, consisting of mu heavy chain + surrogate light chain), which is the developmental checkpoint that normally licenses transition from pro-B to pre-B cell and then to immature B cells in the bone marrow. Without BTK, B cell development arrests at the pro-B stage, producing profound agammaglobulinemia (all immunoglobulin classes absent) with intact T-cell immunity. Recurrent pyogenic bacterial infections begin after maternal antibody wanes at 6-9 months.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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