X-linked agammaglobulinemia (Bruton disease) results from BTK (Bruton tyrosine kinase) mutations. BTK is essential for which specific developmental checkpoint in B-cell maturation?

• A Transition from naive B cell to activated B cell — necessary for BCR crosslinking
• B Somatic hypermutation in germinal centers for affinity maturation
• C Transition from pro-B cell to pre-B cell — signaling through the pre-BCR for heavy chain gene rearrangement ✓
• D Class switch recombination from IgM to IgG in secondary lymphoid organs

Explanation

BTK (Bruton tyrosine kinase) is essential for pre-B cell receptor (pre-BCR) signaling, which occurs when a productively rearranged immunoglobulin heavy chain pairs with surrogate light chain (VpreB + λ5). This signaling drives proliferation, allelic exclusion, and differentiation from pro-B to pre-B to immature B cells. BTK mutations block this checkpoint, resulting in maturation arrest at the pro-B cell stage with absent peripheral B cells and profound hypogammaglobulinemia. This is also why BTK inhibitors (ibrutinib) are effective in mature B-cell malignancies.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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