Ontogeny of murine accessory cells: Ia antigen expression and accessory cell function in <i>in vitro</i> primary antibody responses.

Abstract

Abstract The ontogeny of accessory cell function was studied in an in vitro system measuring primary IgM antibody responses to TNP-KLH. In this system unprimed spleen cells from adult mice produce antibody to soluble TNP-KLH, a response that has been shown to require T cells, B cells, and adherent accessory cells. In contrast, spleen cells from neonatal mice through 2 weeks after birth failed to generate measurable antibody responses in this system. The present study has investigated the functional competence of adherent accessory cells isolated from neonatal spleen by comparing the ability of neonatal and adult splenic adherent cells (SAC) to reconstitute the antibody response of accessory cell-depleted adult spleen cell populations. The results demonstrate that SAC prepared from mice 1, 2, or 3 weeks after birth were consistently less efficient accessory cells than adult SAC for the in vitro generation of antibody responses to soluble TNP-KLH. In experiments employing antigen-pulsed SAC, it was further demonstrated that neonatal SAC were deficient in their ability to function as antigen-presenting cells. These decreased activities were not mediated by demonstrable suppressor cell activity, and thus appear to reflect a defect in accessory cell function. Since it has previously been demonstrated that the accessory cells required for this in vitro antibody response are phagocytic and bear Ia antigens, the ontogeny of la antigen expression on latex-phagocytic SAC was investigated. Immunofluorescence studies utilizing anti-la alloantisera and a monoclonal anti-I-Ak reagent revealed that the neonatal SAC populations contained fewer la-positive latex-phagocytic cells than were present in adult SAC populations. In contrast, no difference was observed in the expression of K region-encoded antigens on adult and neonatal latex-phagocytic SAC. Moreover, greater than 95% of splenic B cells were Ia antigen positive by 7 to 9 days after birth. The ontogenetic rates of expression of Ia antigens on B cells and on latex-phagocytic SAC are therefore distinct and only the latter correlates with the increasing functional competence of spleen cells of increasing age after birth to generate primary antibody responses to TNP-KLH in vitro. Furthermore, since helper T cells appear to recognize TNP-KLH in association with / region-encoded determinants on accessory cells, the relative paucity of la-bearing cells in neonatal SAC populations may explain the functional incompetence of the neonatal spleen and SAC populations.