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Regulation of Antibody Response in Vitro

V. Effect of Carrier-Specific Helper Cells on Generation of Hapten-Specific Memory Cells of Different Immunoglobulin Classes¹

From The Department of Medicine, The Johns Hopkins University, School of Medicine at The Good Samaritan Hospital, Baltimore, Maryland 21212

Abstract

Rabbits were primed with Ascaris antigen (Asc) included in either aluminum hydroxide gel (alum) or in complete Freund's adjuvant (CFA), followed by immunization with DNP-coupled Asc (DNP-Asc) in alum at 4 weeks. Effect of priming with free carrier on the development of DNP-specific (B)² memory cells was analyzed by measuring in vitro antihapten antibody response of their mesenteric lymph node cells to DNP-Asc. The lymph node cells obtained from these animals responded to the antigen in a similar manner as the cells obtained from the animals which were immunized by two 4-weeks-apart injections of DNP-Asc, with respect to: 1) the class distribution of the antibodies between IgG and IgM; and 2) the optimal antigen concentration required for maximal antibody response. These cells formed more IgG antibody than IgM antibody, whereas the lymph node cells obtained after a primary immunization with DNP-Asc formed more IgM than IgG antibody. The optimal antigen concentration required for maximal antibody formation became less when the donors were preimmunized with free carrier, indicating that carrier-specific helper cells may have involved in emergence or selective proliferation of hapten-specific memory cells bearing high affinity receptor. Priming with free Asc in alum showed the carrier effect on the anti-DNP IgE antibody formation, whereas priming with the same antigen in CFA did not. Mesenteric lymph node cells obtained from the alum group formed anti-DNP IgE antibody but the cells from the CFA group failed to do so. No significant difference was observed between the CFA group and alum group with respect to the anti-Asc and anti-DNP IgG antibody titer or to the ability of their lymph node cells to form the IgG antibodies in vitro. The findings indicated that the difference between the two groups in the IgE antibody response is due to some difference in the carrier-specific (T) cell population. The results suggest that carrier-specific (T) helper cells regulate the class distribution and affinity of antihapten antibodies through the exertion of some selective pressure on the generation of hapten-specific (B) memory cells.

Footnotes

¹ This work was supported by Research Grant GB-27682 from the National Science Foundation and a grant from John A. Hartford Foundation. This paper is Publication 75 from the O'Neill Laboratories at The Good Samaritan Hospital.