Selective Roles of Thymus-Derived Lymphocytes in the Antibody Response

Abstract

Our preceding studies indicated that thymus-derived lymphocytes (T cells) primed with a carrier antigen suppressed antibody responses by bone marrowderived lymphocytes (B cells) against a hapten coupled to the homologous carrier, when they were transferred into immunized recipients (1). The degree of suppression in IgM and IgG antibody responses differed depending primarily on the time when suppressor T cells were transferred to the recipients. Thus, it appeared that susceptibility of B cells to the regulatory influence of T cells is inherently different according to the differentiation stages of B cells following antigenic stimulation. The results are in accordance with the widely noted distinction between IgM and IgG antibody responses with respect to their dependency on T cells (2-4).Another important facet observed in the above T-cell-mediated suppression of antibody response is the strict specificity of both T and B cells for the immunizing antigen: to elicit effective suppression T cells must be primed by the carrier on which haptens are coupled. These observations suggest that T cells would specifically influence the emergence and selection processes of B cells by antigen, resulting in the observed preferential suppression of certain populations of antibody-forming cells. It has been generally accepted that antihapten antibodies are heterogeneous with respect to their affinity for hapten, which probably reflects the heterogeneity among B cells (5-8). It has also been noted that the intrinsic affinity of IgM antibodies is usually lower than that of IgG antibodies (9-11). In view of these immunochemical bases, the present experiments were undertaken to study what subpopulations of B cells with regards to the affinity of produced antibody are, in fact, selectively suppressed by the carrier-specific T cells. Materials and MethodsMost essential experimental details have already been described in the preceding paper (1), and only a few points are added here.

Properties of antigen-specific suppressive T-cell factor in the regulation of antibody response of the mouse. I. In vivo activity and immunochemical characterization.

“…Our previous publications (1,2) reported that passive transfer of thymocytes and spleen cells from mice primed with a carrier antigen suppresses the anti- body response of normal syngeneic hosts against a hapten coupled to the homologous carrier . This suppression was found to be clearly antigen specific, and mediated by T cells primed by the carrier antigen .…”

“…Our previous publications (1,2) indicated that thymocytes and spleen cells of mice that had been immunized with a high dose of carrier antigen, when transferred into syngeneic host, could suppress the antibody response against a hapten coupled to the homologous carrier . This suppressive effect was found to be mediated by a population of thymus-derived lymphocytes, whose activity was completely abrogated by the treatment with anti-B and complement .…”

Mechanisms of Tolerance: Role of the Thymus and Persistence of Antigen in Calcineurin-Induced Tolerance of Renal Allografts in MGH Miniature Swine

“…In contrast, when these cells were transferred after immunization with DNP-KLH, antibody formation was not inhibited. These results demonstrated that a peripheral T-cell response was suppressing immunologic response to immunization (50,51). This phenomenon was studied extensively in the 1970s and 1980s, and Castagnoli et al found that the supernatant from antigen-specific suppressive thymoma cells was capable of suppressing an alloreactive response to the same antigen.…”

Low antibody affinity restricted to the IgA isotype in IgA nephropathy

“…Somatic mutation of germ line-derived variable region genes has been shown to be involved in the generation of high-affinity binding sites for subsequent selection by antigen [10]. T cells can control the production of high-and low-affinity responses [37,38], with CD8+ cells playing an important role in the regulation of affinity maturation [39]. Interferon-gamma (IFNy) (compared with IL-1 which only increases antibody levels) has been shown to potentiate antibody affinity in mice, indicatr ing a role played by Thi cells, possibly acting by enhancing MHC class II expression [40].…”