The dysfunction of Tfh cells promotes pediatric recurrent respiratory tract infections development by interfering humoral immune responses

Recurrent respiratory tract infections (RRTIs) are one of the most common pediatric diseases. Although the pathogenesis of pediatric RRTIs remains unknown, ineffective B cell-dominated humoral immunity has been considered as the core mechanism. During the course of pediatric RRTIs, B cell-dominated humoral immunity has changed from “protector” of respiratory system to “bystander” of respiratory tract infections. Under physiological condition, Tfh cells are essential for B cell-dominated humoral immunity, including regulating GC formation, promoting memory B cell (MB)/plasma cell (PC) differentiation, inducting immunoglobulin (Ig) class switching, and selecting affinity-matured antibodies. However, in disease states, Tfh cells are dysfunctional, which can be reflected by phenotypes and cytokine production. Tfh cell dysfunctions can cause the disorders of B cell-dominated humoral immunity, such as promoting B cell presented apoptosis, abrogating total Ig production, reducing MB/PC populations, and delaying affinity maturation of antigens-specific antibodies. In this review, we focused on the functions of B and Tfh cells in the homeostasis of respiratory system, and specifically discussed the disorders of humoral immunity and aberrant Tfh cell responses in the disease process of pediatric RRTIs. We hoped to provide some clues for the prevention and treatment of pediatric RRTIs.