Deficiency of CD40 ligand (CD40L) causes which primary immunodeficiency?

• A. X-linked agammaglobulinemia
• B. Hyper-IgM syndrome
• C. Severe combined immunodeficiency
• D. Wiskott-Aldrich syndrome

Answer: (B)

CD40L on helper T cells provides the crucial signal to B cells via CD40 to drive class-switch recombination and germinal center formation. When CD40L is deficient, B cells can’t switch from producing IgM to other isotypes (IgG, IgA, IgE), so the antibody response remains predominantly IgM and overall IgG/IgA levels are low. This pattern defines Hyper-IgM syndrome, typically X-linked due to CD40L mutations. The other conditions involve different defects (for example, BTK deficiency with very few B cells in X-linked agammaglobulinemia; broad T and B cell defects in SCID; distinct immunoglobulin patterns and features in Wiskott-Aldrich), so they don’t fit the mechanism of CD40L deficiency. Therefore, deficiency of CD40L causes Hyper-IgM syndrome.