Enhanced antibody affinity in sublethally irradiated mice and bone marrow chimeras.

Abstract

In several animal species a sublethal dose of x-rays, from 100 to 200 R on, causes maximum depression of the primary antibody response if antigen is injected 1-2 days after total-body irradiation. The depressive effect of sublethal doses of x-rays is transient, however; recovery starts at 1 week and may be complete 2 months after radiation doses as large as 500-700 R (1).Recovery of the immune system after a supralethal dose of x-rays can be achieved by transplantation of hemopoietic cells. Animals so treated are denominated chimeras because they possess, often for their life span, cells of graft origin (2). Antigenic stimulation of radiation chimeras may result in antibody production by cells of donor type (3). Recovery of the antibody response of bone marrow chimeras is faster in syngeneic than in allogeneic combinations. In some experiments, the antibody response of syngeneic chimeras could attain normal levels when antigen was injected 30-60 days (4) or 60-90 days (5) after bone marrow transplantation. In other experiments, however, the antibody response of syngeneic chimeras immunized 16060 days after transplantation was still subnormal although higher than the response of allogeneic chimeras-of the same age (6). The lower antibody titer observed in allogeneic as compared to syngeneic chimeras was attributed to incomplete repopulation of the immune system, although it could not be ruled out that immunologically competent cells were less efficient in antibody production when stimulated in allogeneic hosts (5). That immunologic mechanisms are abnormally operating in allogeneic bone marrow chimeras was suggested by the finding that these animals, 90-120 days after transplantation, had a decreased ability to synthesize 7S antibodies to certain antigens (7).In all these studies on the antibody response in sublethally irradiated mice and in bone marrow radiation chimeras, antibody affinity was not examined. Affinity, that is, the binding Irradiation. Total-body x-irradiation of the animals was performed as described (9). Mice were either sublethally irradiated (450 R) or lethally irradiated (900 R).Chimeras. Within 2 hr after radiation exposure, lethally irradiated mice were injected intravenously with I ml of a cell suspension containing 1 X 107 nucleated bone marrow cells from normal donors. Suspensions of bone marrow cells were prepared in Eagle's medium as described (9). Allogeneic chimeras were obtained using DBA donors and C3H recipients, and designated DBA/C3H. Syngeneic chimeras were of the following types: C3H/C3H and DBA/DBA. In each strain combination, donors and hosts were of the same sex. In a previous study (5), erythropoietic and antibody-forming cells of all allogeneic chimeras prepared as the present ones and tested 60-150 days after transplantation were of donor type only.Immunization. The antigen used for primary and secondary immunization was dinitrophenyl-keyhole-limpet-hemocyanin (Dnp-KLH), 62 moles of Dnp per mole of KLH, from Calbiochem.Normal C3H and DBA mice, sublethally irradiated C3H m...

Selective Effects of Ionizing Radiations on Immunoregulatory Cells

“…Enhancement of anti-DNP antibody affinity had also been observed in radiation chimeras primed with DNP-KLH 120 days after syngeneic or allogeneic bone marrow transplantation and boosted at different time intervals after priming, as already described (Doria et al 1977a). In contrast to the antibody titer, which was much lower in radiation chimeras than in unirradiated controls, affinity was higher in chimeras than in controls ( Figure 6).…”

“…Some experimental data support the notion that suppressor T cells are radiosensitive before stimulation and become relatively radioresistant after activation. Thus, irradiation of T cells before stimulation with Con A abrogates the generation of non-specific suppressor cells that inhibit an in vitro antibody response to SRBC, whereas the mitogen-activated cells are still able to suppress even after 2000 rad (Rich & Pierce 1973, Dutton 1975. Similarly, the primary response of lymphoid cells transferred from adult donors and stimulated in newborn recipients is enhanced if the recipients are given 350 rad before the cell transfer.…”

IgE Antibodies Produced in Mice Instrumental in Analyses of Antigenicity of Cephalothin Preparation

“…We immunized mice with CET-As together with B. pertus sis or with the treatment of irradiation by y-ray, both of which were known to enhance the formation of IgE antibodies and/or the affinity of the antibodies [7,8,13,29].…”