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  • Title: Antibody production in mice. V. The suppressive effect of anti-carrier antibodies on cellular cooperation in the induction of secondary anti-hapten antibody responses.
    Author: Hamaoka T, Takatsu K, Kitagawa M.
    Journal: Immunology; 1973 Mar; 24(3):409-24. PubMed ID: 4540955.
    Abstract:
    Cooperative induction of secondary anti-hapten antibody responses was studied by using non-cross-reactive carrier proteins, bacterial α-amylase (BαA), Taka-amylase A (TAA) and keyhole-limpet haemocyanin (KLH), and the 2,4-dinitrophenyl (DNP) and benzylpenicilloyl (BPO) groups as haptenic determinants. Lymphoid cells obtained from mice primed with a hapten-carrier conjugate could be effectively stimulated with a hapten-heterologous carrier conjugate, provided that lymphoid cells primed to the heterologous carrier were also present. In the carrier-primed lymphoid cell population, helper activity of thymus-derived cells developed earlier following carrier immunization than did the capacity of antibody-forming cell precursors (AFCP) to produce an effective anti-carrier antibody response upon secondary stimulation. Attempts to generate hapten-specific helper cell activity were unsuccessful. Thus, cells primed to one haptenic determinant failed to exert a helper function with cells primed to a second hapten upon subsequent administration to the two haptens together on the same heterologous carrier molecule. In order to distinguish among carrier determinant specificities which react with thymus-derived helper cells from those which react with bone marrow-derived AFCP, the capacity of various anti-carrier antibodies or antibody fragments to suppress either anti-carrier antibody production alone or together with helper cell function in adoptive secondary anti-hapten antibody responses was tested. In this system, it was found that 7S anti-carrier antibody suppressed the reaction of helper cells and carrier-specific AFCP such that both the anti-hapten and anti-carrier antibody responses were abrogated. By contrast, passively administered 3.5S fragments of anti-carrier antibodies selectively prevented the stimulation of carrier-specific AFCP to produce anti-carrier antibodies, but had no effect on the capacity of carrier-specific helper cells to facilitate the secondary anti-hapten antibody response. As expected, passively administered 7S anti-hapten antibodies selectively abrogated the production of anti-hapten, but not anti-carrier antibodies. These data are discussed in the context of suggesting that distinct determinant sites on carrier molecules are recognized independently by thymus-derived helper cells and by bone marrow-derived AFCP.
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