Maternal Schistosomiasis Hinders B Cell Development Leading to Reduced Humoral Immunity Upon Immunization

Abstract

Abstract Maternal helminth infections are a global public health concern that correlate with altered infant immune responses to childhood immunizations and infection. A mechanistic understanding of how maternal helminth infection alters the immune responses of offspring is critical to improve childhood vaccine regimens in endemic areas, decrease childhood morbidity, and to understand the consequences of specific defects in long-lived immunity. Our murine model of maternal Schistosoma mansoni infection demonstrated that pups born to mothers chronically infected with Schistosoma mansoni have reduced IL-4 production and B cell expansion. This defect continues following tetanus/diphtheria immunization, resulting in impaired immunity. To determine the origin of this humoral immunity defect, we began investigating lymphoid progenitors. We found an increase in the common lymphoid progenitors (CLPs) in the bone marrow of naïve mice from infected mothers. When immunized with a Tetanus/Diphtheria vaccination, there is a significant reduction in expansion of these progenitors in comparison to age matched controls from uninfected mothers coupled with a decrease in bone marrow B cells. RNA sequencing revealed a defect in stem cell pluripotency signaling pathway. Further analysis post-immunization shows a decrease in immature B cells in the bone marrow of pups from infected mothers, suggesting a more exclusive selection process or differential selective pressure, leading to lower B cell frequencies in the draining lymph node. We hypothesize that altered transcriptional regulation at the progenitor level caused by maternal Schistosomiasis is the mechanistic root of long-lived defects in humoral immunity to foreign antigens.