Dual Regulatory Role of the Thymus in the Maturation of Immune Response in the Rabbit

Taniguchi, Masaru; Tada, Tomio

doi:10.1084/jem.139.1.108

Cited by 32 publications

(10 citation statements)

References 40 publications

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“…However, Gershon and Paul [9] demonstrated that T cells indirectly influence the production of high affinity anti-hapten antibodies in response to immunization with hapten-protein conjugates. Furthermore, Taniguchi and Tada [31] stressed the direct action of T cells on antibody maturation with B cells which had already been selected by the antigen and were ready to proliferate and synthesize antibody with the destined affinity. Thus, it is reasonable to assume that antibody affinity reflects the properties of both antigen-stimulated B and T cells.…”

Section: Discussionmentioning

confidence: 99%

“…The affinity of the antibody reflects the properties of B cells rather than those of T helper cells [16], but the helper cells still seem to have some influence on the alteration of the affinity of anti-hapten antibodies [9,18,30,31]. Injection of complete Freund's adjuvant or bacterial lipopolysaccharide (LPS) concomitantly with antigen results in a heightening of the affinity of serum antibody [20].…”

Section: Introductionmentioning

confidence: 99%

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Modulation of Mouse Anti-Trinitrophenyl Plaque-Forming Cell Affinity by Adjuvants or Lectins

Saito

Nakano

Kumazawa

1976

Japanese Journal of Microbiology

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The effects of several kinds of adjuvants or lectins, such as Corynebacterium parvum, dextran, poly AU, poly IC, dibutyryl cAMP, concanavalin A (Con A), phytohemagglutinin (PHA) and pokeweed mitogen (PWM) on anti-trinitrophenyl (TNP) direct plaque-forming cells (PFC) in the spleen of mice and the affinity of antibodies produced by these PFC were examined. The numbers of anti-TNP PFC in the spleens of mice which had been injected with C. parvum 7 days in advance were greater than those in controls after immunization with TNP-coupled heterologous erythrocytes, while the affinity of antibodies released by these PFC was not affected. On the contrary, simultaneous injection of dextran with TNP-erythrocytes did not increase the numbers of splenic anti-TNP PFC, but heightened the affinity of antibodies released by these PFC. Copolymers of nucleotides, poly AU and poly IC, were capable of enhancing splenic anti-TNP PFC responses, but showed almost no altering of PFC affinity. Dibutyryl cAMP did not have any effect on this system. Con A had potencies to both augment the number of anti-TNP PFC and heighten the PFC affinity, while PHA seemed to lack these potencies. Injection of PWM in the presence of antigen increased the number of anti-TNP PFC and heightened slightly the PFC affinity. These results indicate that the heightening of the affinity at the cellular level is regulated in ways different from the augmenting effects on the number of anti-TNP PFC by adjuvants or lectins. These results are discussed in the light of the mode of action of the substances used.The anti-hapten antibodies secreted by antibody-producing cells (B cells) after antigenic stimulation are heterogeneous with respect to their affinity for hapten, and the antibodies with higher affinity increase with time after the stimulation [17,26,29]. The affinity of the antibody reflects the properties of B cells rather than those of T helper cells [16], but the helper cells still seem to have some influence on the alteration of the affinity of anti-hapten antibodies [9,18,30,31]. Injection of complete Freund's adjuvant or bacterial lipopolysaccharide (LPS) concomitantly with antigen results in a heightening of the affinity of serum antibody [20]. LPS is known not only to be a powerful adjuvant [21] but also to have a potency as a polyclonal activator [22].Our previous studies [27] indicated that LPS in the presence of antigenic stimulation has some effect on hapten-specific B precursors in heightening the affinity or in selecting high affinity antibody-producing progeny cells, but the alteration of antibody affinity and the increase in number of antibody-producing cells induced by LPS are regulated by different mechanisms. There are many other adjuvants and mitogens such as Corynebacterium parvum, dextran, polynucleotides and lectins, which can stimulate T or B cells specifically and result in augmentation of immune responses. To examine whether these substances affect the affinity of antibodies secreted from antigenstimulated anti-hapten antibody-pr...

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Modulation of Mouse Anti-Trinitrophenyl Plaque-Forming Cell Affinity by Adjuvants or Lectins

Saito

Nakano

Kumazawa

1976

Japanese Journal of Microbiology

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“…Indeed, Siskind and co-workers (5, 17i 18) and Harel et al (19) have shown that mere nonspecific modifications of the magnitude of antibody response by adjuvant and immunosuppressants do not significantly alter the affinity of the antibody produced in the rabbit, although a high degree of antigenic competition in guinea pigs does affect profoundly the affinity of the produced antibody (19,20). However, Taniguchi and Tada (21) reported that affinity of produced antibody in the rabbit is influenced by the carrier-specific T cells. They found that a relative depletion of T cells by surgical or chemical thymectomy caused a marked enhancement of antibody formation accompanied by a striking increase in antibody affinity.…”

Section: Suppression Of Relative Avidity Of Pfc For Hapten By Carriermentioning

confidence: 99%

Selective Roles of Thymus-Derived Lymphocytes in the Antibody Response

Takemori

Tada

1974

The Journal of Experimental Medicine

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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.

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“…Thus help and suppression are probably mediated by separate functional cell populations. Suppressor cells are shorter lived in the mouse (25) and the rabbit (26) and apparently decline faster after thymectomy than do helper cells. The elegant studies of Cantor and Boyse (27) indicate that different antigens exist on helper and suppressor populations.…”

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confidence: 99%

In vitro studies of the rabbit immune system. V. Suppressor T cells activated by concanavalin A block the proliferation, not the induction of antierythrocyte plaque-forming cells.

Redelman¹,

Scott²,

Sheppard³

et al. 1976

The Journal of Experimental Medicine

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The late B-cell proliferative phase of the in vitro antibody response by rabbit spleen cells is highly susceptible to suppression by activated T cells. The in vitro antisheep erythrocyte plaque-forming cell (PFC) response by spleen cells from normal or primed rabbits can be suppressed by adding concanavalin A (Con A), Con A-prestimulated peripheral blood or spleen lymphocytes, or supernates from Con A-prestimulated peripheral blood lymphocytes. The suppression is not mediated by a direct interaction of Con A with responding cells as shown by the effectiveness of prestimulated cells. Primed spleen cultures remain sensitive to Con A suppression as late as 72 h after initiation, and the addition of Con A after 24-72 h rapidly stops the increase in the number of PFC. T cells are required for Con A addition to be effective but the suppression can be induced at a time when T-helper cells are no longer necessary. Further, the suppressive effect of Con A addition is abrogated by specific antisera to rabbit T cells. We propose that Con A activates suppressor T cells which then exert their effects on proliferating PFC or their immediate precursor B cells. The early inductive or recruitment phase of the response is probably not blocked by suppressor cells. Also, there is an apparent relationship between the number of proliferating B cells and the number of suppressor cells required. Finally, the difficulties in inducing a stimulatory effect by Con A and the prolonged period that Con A addition is suppressive suggests that the rabbit has relatively more and/or longer-lived suppressor cells than the mouse and may be a particularly useful species for studying suppressive phenomena and their mechanisms.

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Dual Regulatory Role of the Thymus in the Maturation of Immune Response in the Rabbit

Cited by 32 publications

References 40 publications

Modulation of Mouse Anti-Trinitrophenyl Plaque-Forming Cell Affinity by Adjuvants or Lectins

Modulation of Mouse Anti-Trinitrophenyl Plaque-Forming Cell Affinity by Adjuvants or Lectins

Selective Roles of Thymus-Derived Lymphocytes in the Antibody Response

In vitro studies of the rabbit immune system. V. Suppressor T cells activated by concanavalin A block the proliferation, not the induction of antierythrocyte plaque-forming cells.

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