Cells involved in the immune response: XI. Identification of the antigen-reactive cell as the tolerant cell in the immunologically tolerant rabbit

Abstract

Previous investigations have disclosed that normal allogeneie bone marrow cells can transfer antibody-forming capacity to irradiated rabbits (1-5). On the other hand, "primed" bone marrow (bone marrow obtained from a donor rabbit 24 hr following intravenous administration of the specific antigen) could not transfer antibodyforming capacity to the antigen with which the marrow donor had been immunized, but could transfer immunocompetence to other antigens (3, 4). It was also demonstrated that the antibody-forming cell in the marrow recipient is of host, not donor, origin (5), thus supporting the conclusion that the immunoeompetent cell in the bone marrow is the antigen-reactive cell and that the bone marrow does not contain any antibody-forming cells (4--7). Furthermore, it was demonstrated that antigenreactive cells, isolated by passage of the normal bone marrow cell suspension through an antigen-sensitized glass bead colnmn, followed by elution of retained cells from the column (eluate), could transfer antibody-forming capacity to an irradiated rabbit, but only toward the antigen used to sensitize the glass beads (2). In contrast, the cells which passed through the antigen-sensitized glass bead column (effluent) lost the capacity to transfer immtmoeompetence with respect to the antigen used to sensitize the beads, but not with respect to other non-cross-reacting antigens (2).These findings suggested a means of indentifying which of the cell types concerned with the mediation of the humoral immune response in the rabbit--the antigen-reactive cell or the antibody-forming ceil--is the tolerant cell in the immunologicaily tolerant rabbit. As shown below, it would appear that the antigen-reactive cell is the one which is unresponsive in the latter animal. Materials and MethodsNew Zealand white rabbits were used throughout this study. The antigens used were human serum albumin (HSA) (Ityland Laboratories, Los Angeles, Calif.) and bovine gamma

Cells Involved in the Immune Response

“…In the latter case, the recipients had been made tolerant to HSA and were tested for humoral antibody formation to HSA follow ing cell transfer. It has previously been demonstrated that the unre sponsive cell in the immunologically-tolerant rabbit is the ARC [6] ; therefore, the recovery of immunocompétence following transfer can be attributed to the acquisition of virgin ARC.…”

“…Therefore, the ARC directed toward the Forssman antigen would have vacated the bone marrow and migrated to these organs where they would react with the Forssman antigen. Since AFC arc probably present in all the lymphoid organs of the normal rabbit [6], an immune response to the Forssman antigen would likely ensue in these gut-associated lymphoid tissues with antibody-forming cells and memo ry cells subsequently detected in these sites. These cells might also spill over into the circulation and would therefore be detected in the blood.…”

“…Furthermore, lymph node, spleen or thymus cells can transfer immunocompetence to an immunologically-tolerant mouse [30,31]. It has been demonstrated that the unresponsive cell in the tolerant rabbit is the ARC, and not the AFC [6]. If it is also the ARC which is affected in the tolerant mouse, then these data favour the spleen and lymph node, in addition to the thymus, as sources of ARC in the mouse.…”

“…sheep erythrocytes) were in- capable of transferring immunocompétence with respect to the antigen used to immunize the marrow donor (sheep erythrocytes) but could still transfer antibody-forming capacity to all other antigens tested, following their transfer to irradiated (800 r) recipients [5]. It was also demonstrated that the cell which synthesizes the humoral antibodies in the irradiated (800 r) recipient is of host, and not donor, origin [1], and that the unresponsive cell in the immunologically-tolerant rabbit is the ARC and not the AFC [6].…”

“…On the basis of these results, and that ARC can be isolated from a suspension of normal rabbit marrow cells by passage of the cells through antigen-sensitized glass bead columns, followed by elution of the specifically-adsorbed cells [7], it was concluded (a) that the cell in the normal rabbit bone marrow which reacts with the antigen in vitro with proliferation and transfers immunocompétence to irradiated (800 r) recipients is the ARC [1,3,[5][6][7], (b) that the ARC vacates the bone marrow following interaction with the antigen in vivo [3][4][5] and (c) that the ARC does not return to the bone marrow following immunization [3]. Since only the normal bone marrow cells of all the lymphoid organs exhibited the capacity to react with antigens in cell culture [3] and since the normal bone marrow cells could transfer immunocompétence to irradiated (800 r) recipients [4,5], it was considered that the bone marrow constitutes the primary, if not the only, source of the ARC in the normal adult rabbit [3,5].…”