A 1-year-old boy has recurrent otitis media and Pneumocystis jirovecii pneumonia. Serum IgG and IgA are very low but IgM is markedly elevated. Flow cytometry shows normal numbers of CD19+ B cells and CD8+ T cells with absent CD40 ligand expression on activated CD4+ T cells. What is the underlying defect?

• A Defective thymic development causing absence of all T cells
• B Failure of VDJ recombination due to RAG1 mutation
• C Failure of class-switch recombination and somatic hypermutation due to defective CD40-CD40L interaction ✓
• D Defective phagocyte oxidative burst allowing intracellular survival of pathogens

Explanation

X-linked hyper-IgM syndrome results from CD40 ligand mutations on the Xq26 locus. Without CD40L engaging CD40 on B cells, T cell help cannot trigger class switching or affinity maturation, so B cells secrete only IgM. Susceptibility extends to opportunistic organisms such as Pneumocystis because CD40 signaling in macrophages is also impaired. RAG defects cause SCID, thymic aplasia removes both CD4 and CD8 cells, and oxidative burst defects define chronic granulomatous disease.

Reference: Abbas, Cellular and Molecular Immunology, 9th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.