A patient with Bruton X-linked agammaglobulinaemia has recurrent encapsulated bacterial infections. The molecular defect is in Bruton tyrosine kinase (BTK), which blocks B-cell maturation at which stage?

• A Immature B cell to mature B cell transition in secondary lymphoid organs
• B Pre-B cell to immature B cell transition (failure of light chain rearrangement signalling) ✓
• C Common lymphoid progenitor to pro-B cell transition
• D Class-switch recombination from IgM to IgG in germinal centres

Explanation

BTK is essential for pre-B cell receptor (pre-BCR) signalling; when heavy chain rearrangement is complete, the pre-BCR complex on pro/early pre-B cells signals via BTK to drive light chain rearrangement, proliferative expansion, and differentiation into immature B cells. BTK deficiency arrests maturation at the pre-B/pro-B stage in the bone marrow, resulting in absent circulating B cells and severe hypogammaglobulinaemia. The block is in bone marrow B lymphopoiesis, not in peripheral activation or class-switch recombination (the latter is defective in hyper-IgM syndrome).

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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