Farm exposure in infancy is associated with elevated systemic IgG4, mucosal IgA responses, and lower incidence of food allergy.

The role of antibodies in protection against food allergy is debated. Here, we designed a longitudinal birth cohort study recruiting participants from an Old Order Mennonite (OOM) community, a traditional farm lifestyle considered to be at low risk for allergic diseases, and participants from urban and suburban Rochester, NY, USA, that were at higher risk for developing allergic diseases. We collected cord and peripheral blood, stool, saliva, and maternal milk samples longitudinally during pregnancy and during the first year of the infant's life to evaluate B cell and antibody responses. Farm exposure led to an accrual of memory and immunoglobulin G-positive (IgG+) B cells, higher titers of plasma IgG and IgA and salivary and fecal IgA in infants, and higher IgA titers in maternal milk. Moreover, OOM infants and their mothers had higher titers of plasma IgG4 and IgA antibodies to egg ovalbumin in maternal milk, respectively, a feature that we found to be associated with lower incidence of egg allergy. Infant systemic IgG4 and IgA were associated with early introduction or more frequent ingestion of lightly cooked egg, respectively, but there was also an effect independent of egg exposure. Several food antigens were detected in cord blood, with in utero exposure potentially explaining the unexpected presence of antigen-specific IgA at birth. These analyses suggest earlier maturation of B cell immunity in farming lifestyle communities.