Subimmunogenic numbers of sheep erythrocytes (2 × 106 SRBC) were injected into young adult (C57BL/6 × DBA/2)F1 and (C57BL/6 × C3H/He)F1 mice 4 days before the transfer of 2 or 1.25 × 106 spleen cells into irradiated syngeneic recipients. This procedure greatly enhanced the anti-sheep or anti-TNP antibody responsiveness of spleen cells to rechallenge with fully immunogenic numbers (5 × 108) of SRBC or TNP-conjugated SRBC, respectively. The anti-sheep response was accelerated, prolonged, and augmented in terms of the numbers of plaque-forming cells (PFC) generated in recipient spleens. Since the augmentation was considerably greater for IgG than for IgM PFC, the value of IgG:IgM ratios became >1. Low-dose priming caused the number of detectable antigen-sensitive units (ASU) to rise in the spleen: on day 4, the augmentation factors were 2.2 for IgM and 7.5 to 8.4 for IgG ASU, but the numbers of PFC generated by each unit remained the same.

Of the cell types constituting splenic ASU (T and B cells, macrophages), peripheral T lymphocytes were the most likely candidates for mediating the effect of priming. The reasons are: a) low doses of antigen preferentially activate T cells (11–15); b) low-dose carrier priming with SRBC augmented both the anti-sheep and the anti-S-TNP responses; c) addition of thymocytes to unprimed spleen cells moderately augmented anti-sheep responses; d) antigens cross-reactive with SRBC at the level of T but not of B cells were effective in priming for anti-S-TNP responses; e) Bordetella pertussis, an adjuvant requiring T cells, was also effective in this system. The possibility that low-dose priming induced quantitative as well as qualitative changes in the T subpopulations required for helper activity (helper and amplifier cells) was discussed.

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