In X-linked agammaglobulinemia, which immune cells are deficient?

• A. T cells
• B. B cells
• C. Natural killer cells
• D. Macrophages

Answer: (B)

In X-linked agammaglobulinemia, the problem is a block in B cell development due to a mutation in the BTK gene, which encodes Bruton's tyrosine kinase. BTK is essential for signaling that allows B cells to mature from the pre-B stage in the bone marrow. Without functional BTK, B cells fail to mature and are not released into the bloodstream, so there are very few circulating B cells and virtually no antibodies produced. This leaves humoral immunity severely impaired, with markedly low levels of all immunoglobulin isotypes.

Because this defect specifically halts B cell maturation, T cells, natural killer cells, and macrophages are typically present and functional. That’s why the hallmark of this condition is a deficiency of mature B cells rather than a general deficiency of all lymphocytes or innate immune cells. Laboratory clues include very low or absent circulating B cells (for example, CD19+ or CD20+ cells) and profoundly reduced serum IgG, IgA, and IgM. Clinically, patients experience recurrent bacterial infections due to lack of antibody-mediated protection.