Bruton agammaglobulinemia results in the absence of immunoglobulins due to a defect in which process?

• A. T cell maturation
• B. B cell maturation
• C. Complement activation
• D. Antibody class switching

Answer: (B)

Bruton agammaglobulinemia is a defect in B cell development. The BTK signaling pathway is essential for B cells to mature from early precursors in the bone marrow to functional, immunoglobulin-secreting cells. When this process is blocked, there are few or no mature B cells to become plasma cells, so immunoglobulin production drops dramatically and circulating antibodies are absent. T cell development occurs independently in the thymus, so T cells are typically normal, and the antibody deficiency isn’t due to problems with complement activation. Even though class switching is a process B cells can perform after activation, there are no mature B cells to undergo switching in the first place, leading to very low immunoglobulin levels. This explains the early-life susceptibility to recurrent bacterial infections seen in Bruton agammaglobulinemia.