Immunological unresponsiveness to native dextran B512 in young animals of dextran high responder strains is due to lack of Ig receptors expression. Evidence for a nonrandom expression of V-genes.

Abstract

Young mice of dextran high responder strains were found to be complete nonresponders to the alpha-1-6 epitope of dextran during 30-40 days after birth. They also failed to respond to thymus-dependent dextran-protein conjugates. Cells from young and adult mice were activated equally well to polyclonal antibody synthesis by the polyclonal B-cell-activating property of dextran. There was no age difference in the immune response to haptens conjugated to dextran, indicating that dextran can function as an efficient carrier also in young mice. Unresponsiveness could not be attributed to suppressor T cells or to a suppressive environment in young animals, as shown by transfer experiments, in which living or irradiated cells from young and adult mice were admixed in various ways and transferred to irradiated recipients of different ages. Cells from young mice did not affect response of adult cells (and the reverse), nor did the age of the irradiated recipient influence the response. When lymphocytes from young and adult mice were polyclonally activated in vitro by lipopolysaccharide, only cells from young mice failed to synthesize antibodies against the alpha-1-6 epitope of dextran, although they produced antibodies of all other specificities tested for. It was concluded that young animals fail to express immunoglobulins directed against the alpha-1-6 epitope during the first 30-40 days after birth. Since the mice possess the VH gene coding for antibodies against this particular epitope, it was concluded that the timing of V gene expression is regulated during development, possibly at the V-C gene translocation level.

Genetic and temporal control of neonatal antibody expression.

“…Although mechanisms have been defined that can readily account for an extraordinarily diverse antibody repertoire (1-7), previous studies have indicated that neonatal mice have a relatively limited repertoire and that repertoire diversity is gradually acquired in a highly reproducible manner within an inbred murine strain (21)(22)(23)(24). To investigate the characteristics of early neonatal antibodies and probe the mechanisms that may be responsible for repertoire acquisition, we have established two hybridoma cell lines derived from neonatal B cells antigenically stimulated in an CONTROI, OF NEONATAL ANTIBODY EXPRESSION irradiated adoptive host.…”

“…Among the most striking features of the immune mechanism is the extraordinary reproducibility of repertoire expression (19)(20)(21)(22)(23)(24). Thus, in spite of the extremely complex mechanisms available for diversification and clonotype selection, repertoire sharing appears to be the rule among genetically identical individuals.…”

“…Thus, in spite of the extremely complex mechanisms available for diversification and clonotype selection, repertoire sharing appears to be the rule among genetically identical individuals. This is particularly true in situations where the repertoire is limited such as in genetically identical frogs (19), bursectomized chickens (20), and, most importantly, neonatal mice (21)(22)(23)(24). Additionally, where it has been possible to evaluate the expression of clonotypes that occur in high frequency, or even rare clonotypes that are idiotypically identifiable, adult mice of the same strain apparently share repertoire (25)(26)(27)(28)(29)(30)(31)(32)(33).…”

Immune response of neonates elicited by somatic transgene vaccination with naked DNA

“…Based on these data and theoretical considerations, Burnet (3) proposed that the ability to distinguish self from non-self results from the deletion of self reactive clones during the early stages of the immune system development. This concept was supported by experiments that showed an impaired ability to produce specific antibodies following neonatal injection of large amounts of foreign antigens (4,5) or antibodies specific for idiotypic, allotypic or isotypic determinants of Ig receptors (6)(7)(8). Furthermore, Etlinger and Chiller (9) showed that aggregated human gammaglobulin, a highly immunogenic T-dependent antigen in euthymic mice, was able to induce immune specific unresponsiveness when injected into newborn mice.…”

“…Neonatal injection with antibodies specific for immunoglobulin (Ig) antigenic determinants caused a long lasting suppression of the B cells that express the corresponding determinant (6)(7)(8). Furthermore, injection of large amounts of bacterial polysaccharides (4,5) or T-dependent antigens (9) impaired the subsequent synthesis of specific antibodies.…”