Cells Involved in the Immune Response

Abstract

Bone marrow cells obtained from rabbits of one allotype were injected into irradiated rabbits of a different allotype. The recipients were also injected with sheep red blood cells, and their spleen cells were tested for plaque-forming capacity 7 days later. Spleen cells of all recipients gave large numbers of plaques as did spleen cells incubated with antiserum, directed toward donor allotype. However, incubation of the recipient spleen cells with antiserum directed toward recipient allotype completely suppressed plaque formation. These results demonstrate that antibody-formation in irradiated recipients of transferred lymphoid cells is a property of the recipient animal and that the antibody-forming cell is relatively irradiation-resistant. It was also demonstrated that only viable normal bone marrow cells are capable of transferring antibody-forming capacity to irradiated recipient rabbits. Neither sonicates nor heat-killed preparations of normal rabbit bone marrow cells possessed this capacity.

Cells Involved in the Immune Response

“…The data presented here, demonstrating a specific interaction between antigen and antigen-reactive cells in normal rabbit bone marrow, and the isolation of the latter cells, confirm previous findings concerned with the immunological role of the bone marrow (1)(2)(3)(4)(5)8). It has previously been noted that normal rabbit bone marrow cells react with blastogenesis and mitosis as a result of in vitro stimulation with a great variety of antigens (1,2), and that bone marrow cells obtained from a rabbit injected with the antigen only 8-24 hr prior to sacrifice (primed bone marrow) lose the capacity to respond to the specific immunizing antigen in vitro, but not to other antigens (2).…”

“…pretation of our previous data is that the reaction of normal bone marrow cells with antigen in vitro has nothing to do with immunocompetence but is simply an incidental interaction facilitated by the conditions of the experiment. The findings reported in recent studies (8), demonstrating the antigen-reactive nature of the immunocompetent cells in normal bone marrow, and the present demonstration that the antigen-reactive cells in normal b~ne marrow interact with the antigen adsorbed onto glass beads and are capable of expressing immunocompetence following their elution from the glass beads, support only the first concept presented above. These data, therefore, strongly indicate that antigen-reactive cells in fact migrate out of the bone marrow in the rabbit following contact with the antigen.…”

“…Furthermore, since irradiated mice do not exhibit an immune response if given only thymus antigenreactive cells and antigen (34)(35)(36)(37)(38)(39), it would appear that the antibody-forming cell in the mouse is irradiation-sensitive, unlike that in the rabbit, which is irradiation-resistant (8). An alternative hypothesis, which must be ruled out experimentally, is that the antibody-forming cell in the mouse is of recipient origin and is irradiation-resistant to 800 R, as in the rabbit (8), but that another cell type, other than the thymic antigen-reactive cell, normally resident in the bone marrow is required in order to mediate the immune response in the mouse. The sequence of cellular events mediating the primary humoral immune responses in the rabbit and the mouse, as postulated by the present investigators, is presented in Fig.…”

“…Certainly, the reaction of the normal bone marrow cells with antigen cannot be attributed to interaction of the antigen with antibody-forming cells (which would be expected to possess specific immunoglobulin molecules on their surfaces), since previous investigations have disclosed that the immunocompetent cells residing in normal bone marrow are antigen-reactive cells and not antibodyforming cells (actual or potential) (8). Thus, it would appear that the antigenreactive cell exercises its function on the basis of specific antibodv-like sites on its surface capable of reacting with the antigen.…”

“…However, spleen cells of irradiated rabbits given "primed" allogeneic bone marrow cells and immunized with sheep erythrocytes were incapable of producing plaques in vitro (5). It was further demonstrated, utilizing the technique of inhibition of plaque formation with antiallotype antiserum, that the antibody-producing or plaque-forming cell in the irradiated recipient rabbit is irradiation-resistant and is of host, not donor, origin (8). This cell is therefore not derived from any of the allogeneic bone marrow cells transferred.…”