Intergenerational protective anti-gut commensal immunoglobulin G originates in early life

Significance

This work describes the time-limited, early-life, physiologic development of protective maternal anti-gut commensal IgGs. The antibodies persist after weaning and are passed to the next generation. Perturbations during the mother’s infancy lead to a loss of protection against infections of enteric origin in their offspring. These long-lasting plasma cells form in the intestinal immune compartment and provide passive protection to the offspring during enteric infections by preventing secondary systemic dissemination of gut commensals.

Abstract

Maternal immunoglobulins of the class G (IgGs) protect offspring from enteric infection, but when, where, and how these antibodies are physiologically generated and confer protection remains enigmatic. We found that circulating IgGs in adult mice preferentially bind early-life gut commensal bacteria over their own adult gut commensal bacteria. IgG-secreting plasma cells specific for early-life gut bacteria appear in the intestine soon after weaning, where they remain into adulthood. Manipulating exposure to gut bacteria or plasma cell development before, but not after, weaning reduced IgG-secreting plasma cells targeting early-life gut bacteria throughout life. Further, the development of this anti-gut commensal IgG response coincides with the early-life interval in which goblet cell–associated antigen passages (GAPs) are present in the colon. Offspring of dams “perturbed” by B cell ablation or reduced bacterial exposure in early life were more susceptible to enteric pathogen challenge. In contrast to current concepts, protective maternal IgGs targeted translocating gut commensals in the offspring, not the enteric pathogen. These early-life events affecting anti-commensal IgG production have intergenerational effects for protection of the offspring.