Delayed and deficient establishment of the long-term bone marrow plasma cell pool during early life

Early life antibody responses are characterized by a rapid decline, such th at antigen-specific IgG antibodies decline to baseline levels within months following infant immunization. This generic observation remains unexplaine d. Here, we have analyzed the induction and organ-localization of antigen-s pecific IgG antibody-secreting cells (ASC) following immunization of 1-week -old or adult BALB/c mice with tetanus toxoid (TT), a T-dependent antigen. Early life priming induced only slightly lower numbers of TT-specific IgG A SC in the spleen, and these reached adult levels following repeat immunizat ion. In contrast, early life immunization generated much fewer bone marrow plasma cells than in adults, even after boosting. A similar limitation of t he natural development of the bone marrow pool of ASC was observed. Transfe r experiments with adult or early life spleen ASC indicated limited homing of TT-specific adult ASC to the bone marrow of 4-week-old mice as compared to adult recipients, whereas homing patterns were similar when early life o r adult ASC were transferred into adult recipients. These observations sugg est that a limited bone marrow B cell homing capacity and, as a result, rel atively deficient bone marrow ASC responses, are critical factors which may explain the limited persistence of IgG antibodies to T-dependent antigens in early life.