Sex differences in the early life correlates of natural antibody concentrations

Abstract

Innate-like B1a lymphocytes arise from long-lived progenitors produced exclusively by fetal stem cells. Any insults coinciding with this early lymphopoietic wave could have a permanent impact on the B1a population and its unique protein products, the natural antibodies (NAb). We investigated early life nutritional influences on NAb concentrations of pre-adolescent children (n=290) in rural Nepal for whom we had extensive information on exposures from pregnancy and early infancy. Infant size and growth were strongly associated with NAb concentrations at 9–13 years of age among males (e.g., for neonatal weight: βBOYS=0.43; P<0.001), but not females (e.g., for neonatal weight: βGIRLS=−0.16; P=0.26). In females, season of birth was associated with NAb concentrations, with marked reductions among girls born during the pre-monsoon (March–May; βGIRLS=−0.39; P=0.01) and pre-harvest (September–November; βGIRLS=−0.35; P=0.03) seasons. Our findings suggest that nutritional or other environmental influences on immune development may vary by sex, with potential consequences for immune function during infancy and long-term risk of immune-mediated disease.