A 4-year-old boy has recurrent pyogenic infections since birth, with absent lymph nodes and tonsils. Flow cytometry shows absence of all B cells (CD19–) but normal T cells. Serum immunoglobulins are undetectable. This presentation is consistent with a defect at which developmental stage?

• A Failure of class-switch recombination in mature B cells
• B Deficiency of IL-7 receptor blocking T-cell development
• C CD40L mutation on T cells preventing B-cell activation
• D Defective BTK (Bruton's tyrosine kinase) preventing pro-B to pre-B transition ✓

Explanation

X-linked agammaglobulinaemia (Bruton's disease) is caused by mutations in BTK, an enzyme essential for signalling through the pre-B cell receptor. This blocks development at the pro-B to pre-B transition in the bone marrow, resulting in near-complete absence of mature B cells and all immunoglobulin classes. T-cell numbers are normal. Onset of recurrent pyogenic infections occurs at 6–9 months when maternal antibodies wane. Class-switch defects (HIGM) allow IgM but not IgG/IgA production. IL-7R deficiency affects T-cell development. CD40L deficiency (HIGM type 1) permits B cells but no IgG switch.

Reference: Ananthanarayan & Paniker's Textbook of Microbiology, 11th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.