The reason why some pediatric patients exhibit defective antibody responses, which can lead to recurrent respiratory tract infections and increased allergic responses, is reported this week in a study published in Nature Immunology. These findings may lead to better vaccine development in general and treatments for these immunodeficient patients.
Children harboring DOCK8 mutations encounter recurrent infections due to poor antibody production. What little antibody that is produced in these patients is skewed towards a class of antibodies called IgE, which are associated with allergic responses. Hence these patients are both immunodeficient and have greater susceptibility to severe allergies.
Raif Geha and colleagues looked at the molecular basis for DOCK8 protein function in antibody-producing B immune cells. They found that signaling cascades involving the adaptor protein DOCK8 are required for normal antibody production and generation of B cell memory responses. DOCK8 serves as a platform linking innate signaling molecules, in particular those utilizing MyD88, to downstream kinases that activate the transcription factor STAT3. Disrupting the DOCK8-MyD88 interaction and activation of STAT3 leads to similar antibody production defects.