Primary response to lysozyme (HEL) and HEL-LPS in neonatal A/J mice: presence of characteristic adult pattern of regulatory idiotype and fine specificity restriction.

The adult primary murine plaque-forming cell (PFC) response to hen egg-white lysozyme (HEL) is characterized by a predominant idiotype (IdXE) (congruent to 50% of population) and a predominant specificity (congruent to 50% of population) for a determinant dependent on the 3 amino-terminal residues of HEL (TIP-dependent PFC). IdXE and TIP specificity, however, are not congruent: approximately 1/3 of each population do not overlap (1). To determine whether these characteristics result from a prolonged selection process during development, we compared the neonatal A/J response profile to HEL-CFA with the adult A/J response and found that the adult pattern was present for mice immunized as early as 5 days of age. At 5 days, A/J splenic PFC were 80% TIP dependent, 71% IdXE positive compared to the adult levels of 56% (+/- 14) TIP dependent, 43% (+/- 19) IdXE positive. To attempt to address the B cells directly and avoid the need for antigen-specific T-dependent processes, we studied the PFC response to HEL-LPS conjugates in adult and 12-day-old A/J mice. At the earliest age studied (12 days), the indirect splenic PFC had similar idiotypy and specificity as the adult, and the response was similar to that induced by HEL-CFA. Although the absolute IgM PFC level was equal in adult and neonate, only 11% of the adult PFC response was IgM while a large proportion of the 12-day-old HEL-LPS response was IgM. This IgM PFC response was also characterized by the same idiotypy and specificity as the IgG PFC response. These results suggest that the characteristic adult mosaic of specificity and idiotypy in the anti-HEL response may exist prior to antigenic stimulation since it occurs as early as 5 days after immunization and in the IgM PFC responses. Although IdXE predominance may merely reflect the germ line repertoire, T cells may also be involved in an idiotype-based selection, the mechanism of which has not been determined.