The primary PFC response to the protein antigen hen egg lysozyme (HEL) is first detectable at 10-12 days of age in A/J mice. The primary PFC spleen response in these young animals is similar to the adult response in terms of idiotypic and fine specificity characteristics. Approximately 50% of the PFC express the predominant idiotype IdXE and approximately 50% have a requirement for the 3 amino terminal amino acids of HEL (= TIP specificity) although these groups are not congruent. This early response with will-defined characteristics provides an excellent model for studying the effect of maternal antibody on the developing immune response. Our preliminary studies suggest that transplacental and postnatal transfer via colostrum and milk of an IdXE positive anti-HEL monoclonal antibody from A/J mothers to their offspring results in profound suppression of the developing A/J response to HEL. This observed suppressive effect may represent one of the pathways by which idiotypic regulation is manifested in the developing animals. This hypothesis will be tested by administering IdXE positive monoclonal antibody to mothers prior to and after delivery in various dosages and the nature and extent of suppression will be examined in the response of offspring to HEL-CFA. These IdXE experiments will be expanded to direct manipulation of the neonate in order to determine windows of susceptibility to idiotypic manipulation. To determine if the suppressive effect from IdXE positive anti-HEL antibody is the direct result of IdXE antibody or the result of an anti-idiotypic antibody response to IdXE, we plan to administer an IgM IdXE positive monoclonal antibody to the mothers. Finally, we wish to examine the target cell in the offspring of the IdXE monoclonal antibody. Adoptive transfer experiments will be done to further delineate T or B cells as the effector or target cell for the maternally induced suppression. Ly 1+ B cells are found in large numbers in the fetal and neonatal mouse and may be important regulatory cells in the neonate for establishing the idiotypic repertoire of the developing animal. We will further expand our studies to examine the role of T cell subpopulations and Ly 1+ B cells in the observed suppression. In addition to idiotypic manipulation of mothers with monoclonal antibody we will also by study the effect of prior immunization of the mother on the idiotypic repertoire of the developing neonatal response to HEL.
| Jelonek, M T; Brust, J L; Song, C H et al. (1993) Maternal HEL immunization has no lasting effects on the immune response of offspring to immunization with hen egg-white lysozyme. Cell Immunol 148:422-34 |
| Song, C H; Calandra, G B; Miller, A et al. (1991) Evidence for idiotypic sharing between conventional and naturally activated B cells. Eur J Immunol 21:2005-10 |
| Song, C H; Calandra, G B; Palmer, C J et al. (1990) Inhibition of offspring response to HEL-CFA by administration of anti-HEL MAB to the mother is not related to the predominant idiotype, IdXE, or specificity of the MAB. Cell Immunol 131:311-24 |
| Keller, M A; Kaplan, M A; Kenyon, N S et al. (1989) 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. Cell Immunol 119:143-52 |
