In vitro antibody response to a distinct antigenic determinant of Escherichia coli beta-D-galactosidase. Effect of antigen dosage and co-cultivation of lymph node fragments on peak titres and duration of antibody synthesis

Abstract

The anti-β-D-galactosidase activating antibody response in lymph node fragment cultures was investigated in an attempt to understand the mechanism determining the magnitude of an immune response towards a natural hapten, which occurs only once in each antigen molecule, under in vitro conditions that preserve the histology of the responding tissue. Fragments were individually challenged for defined time periods, and washed; cultures with one and two fragments were then set up. Co-cultivation of fragments produced titres higher than predicted from results in single fragment cultures. This happened even when the latter cultures produced low titres because of excessive antigen dosages. Co-cultivation of fragments also improved the duration of the antibody response. These effects appeared to correlate with the number of memory cells present in the fragments at the beginning of the cultures. These observations, together with data obtained by manipulating different doses and times of antigen exposure suggest that collaboration between cells and determinants with different specificities may occur, not only in the initial induction, but also in the sequential stimulation of antibody-forming clones. It is postulated that the co-operative mechanism shown to act in the initiation of the antibody response by cell suspensions toward polyvalent artificial conjugates may also operate when intact lymphoid tissue is reached by a single bacterial determinant in its natural molecular configuration