The responses to one or to two injections of antigen (referred to as "primary" and "secondary" responses, respectively) by lethally irradiated LAF1 mice reconstituted with syngeneic neonatal liver cells plus adult thymus cells are compared with the responses of irradiated mice reconstituted with adult spleen and thymus cells. In every case the primary response by mice reconstituted with neonatal B cells is of restricted heterogeneity of affinity and low average affinity as compared with the

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... onse of animals reconstituted with adult spleen as the source of B cells. The secondary responses by mice reconstituted with adult spleen cells are all highly heterogeneous and of high affinity. The secondary responses to Ova, BSA, DNP-BGG, and the F(ab′)2 fragment of HGG by mice reconstituted with neonatal liver are highly heterogeneous and of high affinity, like those of animals reconstituted with adult spleen. In contrast, the secondary responses to HGG and BGG by mice reconstituted with neonatal liver are of low affinity and restricted heterogeneity as compared with the secondary responses of mice reconstituted with adult spleen cells. Thus, the immune responses of immature B cells to heterologous immunoglobulins differ from their responses to other T-dependent antigens. This difference may be related to some property of the Fc portion of the heterologous immunoglobulin. In addition, the data indicate that with most of the antigens studied a high affinity memory B cell population can be selectively expanded in lethally irradiated mice reconstituted with neonatal liver despite the fact that their primary responses lack detectable high affinity PFC. This suggests that the failure of mice reconstituted with neonatal or fetal B cells to produce a high affinity primary PFC response may reflect an inability of the immature B cells to differentiate into antibody-secreting cells.