An Infant Is Admitted to the Hospital with a History

Essay

An infant is admitted to the hospital with a history of recurrent and persistent bacterial infections. His physician suspects he has an immunodeficiency disease, and obtains a sample of the patient's peripheral blood. The white blood cells are analyzed by antibody staining followed by flow cytometry, and the results are shown in Figure.

To determine the origin of the peripheral blood cell defect, a bone marrow biopsy is taken from the patient and compared to a healthy control, as shown in Figure.

To obtain additional information, bone marrow cells are treated with a chemical that permeabilizes the cell membrane, allowing antibodies to enter the cells and bind to their target antigens within the cells, a technique known as ‘intracellular staining’. The results of this analysis are shown in Figure .

a) What are populations 1, 2, and 3 in Figure?
b) In the analysis of cell surface expression (non-permeabilized bone marrow cells), what are the IgM^lo Igκ⁺λ^neg cells as indicated by the arrow in Figure?

c) What is the most likely defect causing the patient's immunodeficiency?
The results shown above indicate a specific defect in B cell development. To help identify the defective or missing protein in the patient's developing B cells, bone marrow cells are isolated and protein lysates are prepared for immunoblotting. A series of antibodies are tested and the results are shown in Figure.

d) Given the results from the immunoblotting experiments, what is the most likely candidate molecule (or type of molecule) responsible for the patient's immunodeficiency disease?