X-linked agammaglobulinemia (XLA) results from BTK gene mutation. The developmental block in B-cell maturation in XLA occurs at which stage?
- A At the naive B-cell to plasma cell differentiation step
- B At the germinal center reaction causing failure of class switching
- C At the pre-B cell stage — failure of pro-B to pre-B transition due to absent BTK signaling ✓
- D At the hematopoietic stem cell level — combined B and T cell deficiency
Correct answer: C. At the pre-B cell stage — failure of pro-B to pre-B transition due to absent BTK signaling
Explanation
BTK (Bruton tyrosine kinase) is essential for pre-BCR signaling required for the pro-B to pre-B cell transition in bone marrow. Without BTK, B-cell development arrests at the pro-B/pre-B stage, resulting in virtual absence of mature B cells and all immunoglobulin isotypes. T-cell numbers are normal. Absence at the stem cell level would cause SCID (both B and T cell deficiency). Class switching failure characterizes hyper-IgM syndrome (AID or CD40L deficiency).
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.