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 infection and inflammation alters the immune responses of offspring is lacking but is critical to decrease childhood morbidity and to understand the consequences of specific long-lived immunity defects. Using our model of maternal Schistosoma mansoni infection, we have shown that murine pups born to mothers chronically infected with Schistosoma mansoni have reduced responses to vaccinations, corresponding to what has been reported in humans. To determine the origin of this humoral immunity defect, we began investigating the plasticity and functionality of progenitors of lymphoid cells critical for a protective humoral response. We found an increase in the common lymphoid progenitors (CLPs) in the bone marrow of pups from Schistosome infected mothers, but a marked decrease in immature and transitional B cells in male mice, indicating sex-specific limitations during B cell maturation. Using single cell V(D)J sequencing, we found only male pups from infected mothers have a more restricted repertoire compared to male mice from uninfected mothers after immunization, leading to decreased antigen-specific B cells in the germinal center of the draining lymph node. We hypothesize that epigenetic regulation of key immune genes is the mechanistic root of long-lived defects in humoral immunity to foreign antigens during maternal Schistosomiasis.

Supported by a grant from NIH (R01 AI135045)