Benefits and burden of the maternally-mediated immunological imprinting

Abstract The ontogenetic development of both the immune and the nervous system entirely depend on external environmental signals that induce a lifelong learning process. The resulting collective immunological knowledge about the external world is transmitted in an epi-genetic fashion to the offspring, but only from the maternal and not the paternal side, with maternal IgG as the main transgenerational vector. As products of thymus-dependent responses, maternal IgG have undergone immune maturation by somatic hypermutations and are, therefore, acquired immunological phenotypes representing a great deal of the mother's immunological experience. During a limited neonatal imprinting period, maternal antibodies induce T cell-dependent idiotypic responses. These exert up to life-long determinative influences which may even be dominant over seemingly genetic predispositions. Such long-term immunological imprinting effects can be detected as (a) selection of the adult T and B cell repertoires, (b) anti-microbial protection by antigen-reactive antibodies (idiotypes) and anti-idiotypes, (c) allergen-specific suppression of IgE responsiveness by allergen-reactive IgG idiotype or corresponding anti-idiotype and (d) induction of autoimmune diseases by maternally-derived autoantibodies. Hence, immunological imprinting by maternal IgG antibodies will mostly be beneficial, but in case of autoantibodies can also be a burden for the initial development of the nascent immune system.