Cells Involved in the Immune Response

112

Combination between immunogen and antibody molecules present on the relevant antigen-reactive cell(s) is commonly considered an early, essential step in the induction of detectable, high-rate antibody formation. Lymphocytes have been shown to display immunoglobulin-like molecules on their outer cell surface (1-3) and various methods have demonstrated a selective adsorption of antigen to the surface of a minority of the lymphoidal cell population (4-8). The increase of the number of reactive cells in such systems after immunization (4-10) and the specific inhibition of the reactions by blocking antigen (7,8) indicate that lymphoidal cells can display antibody activity on their surfaces. Direct demonstration that these surface receptors could be linked to potential immune capacity of the cells carrying the surface antibodies has come from experiments where filtration of immunologically competent cells through antigen-coated columns was carried out (11,12). In such experiments, specific elimination of the antigen-reactive cells directed against the antigen used for coating the column was obtained as indicated by the reactivity of the passed cells.Since we believe that preformed cell-bound antigen-specific receptor molecules are of prime importance during the induction of immune processes, we have tried to obtain further information by using antigen-coated columns. We have applied the technique to nonimmunized lymphocytes. Emphasis was put on analysis of the size of the antigen-combining site of the receptors by the use of columns coated with different hapten-carrier complexes. Furthermore, investigations were made to explore whether cells potentially capable of producing antibodies of different immunoglobulin classes can be separated in a similar manner. Evidence for the existence of preformed receptors on potential antibody-forming cells directed against complex antigens, as well as against chemically well defined substances of haptenic nature will be presented. The theoretical implications of the findings will be discussed.

Section: Discussionmentioning

confidence: 82%

Separation of Normal and Immune Lymphoid Cells by Antigen-Coated Columns

Wigzell

Mäkelä

1970

112

“…In a very recent article, however, results have been presented on the separation of antigen-sensitive normal rabbit bone marrow cells on antigen-coated columns followed by an analysis in vivo of their immune potential after transfer into allogeneic rabbits (9). In disagreement with our results (7,8,15, and the present article), they report a close to 50-fold absolute increase in specific immune reactivity of the retained cells, indicating not only a passive enrichment of the administered antigen-reactive cells by the column, but also a significant specific stimulation of the immune reactivity of the column-administered cells by the column antigen (9).…”

Section: Discussionmentioning

confidence: 99%

In Vitro Induction of Specific Unresponsiveness of Immunologically Reactive, Normal Bone Marrow Cells

Singhal

Wigzell

1970

Normal rabbit bone marrow cells have been studied according to their immunological reactivity in vitro. The test system involved stimulation by antigen after the subsequent stimulation into cellular proliferation by measuring the uptake of tritium-labeled thymidine. Specific separation of immunological reactivity was obtained by filtration of cells through antigen-coated bead columns. All experimental evidence supported the view that this separation was due to the existence of preformed antibody molecules on the outer cell surface of the antigen-recognizing cells. The response to antigenic stimulation was shown to be strictly dose related and, using supraoptimal concentrations of one antigen, no increased DNA synthesis was recorded. That this state of unresponsiveness represented a state of immunological paralysis was indicated by the normal response of these cells to stimulation by a second antigen in optimal concentration. Thus both methods, cell separation on antigen-coated columns or induction of specific unresponsiveness by antigen in vitro, can produce a cell population specifically devoid of cells reactive against a given antigen.

“…For example, since the two immunopotent portions of the (Phe, G)-Pro--L macromolecule appear to be under separate genetic regulation (6), one can systematically investigate the cellular manifestations of this type of genetic control in relation to problems such as the recognition of the immunogen, the commitment of immunocompetent precursor cells for a given specificity, the nature of the lymphoid organs exhibiting the phenotypic expression of the defect, and the possible significance of histocompatibility loci in the development of the immune state. Although some of the above immunological questions have been studied using heterologous erythrocytes (10)(11)(12)(13), the large number of determinants contributed by such antigens makes an already complex series of events even more difficult to comprehend.…”

mentioning

confidence: 99%

Cellular Basis of the Genetic Control of Immune Responses to Synthetic Polypeptides

Shearer

Mozes

Sela

1971

DBA/1 mice are high responders to the (Phe, G) determinant of the synthetic polypeptide (Phe, G)-Pro--L, whereas SJL mice respond well to the Pro--L region of this macromolecule (6). In order to determine whether the phenomenon described above is related to the number of antigen-sensitive units detected for both specificities, and whether responses to these determinants can be transferred independently, graded and limiting inocula of spleen cells from SJL, DBA/1, and F1 donors were injected into X-irradiated, syngeneic, recipient mice with (Phe, G)-Pro--L. By this approach, one antigen-sensitive unit specific for (Phe, G) was detected in 1.7 x 106 and 8.5 x 106 spleen cells from immunized and nonimmunized DBA/1 donors, respectively. In contrast, one (Phe, G) relevant precursor was detected in 20 x 106 SJL spleen cells, irrespective of whether the donors had been immunized. On the other hand, for the Pro--L specificity, one limiting splenic precursor was found in 1.3 x 106 and in 3.4 x 106 cells for immunized and nonimmunized SJL donors, respectively; whereas one response unit was estimated for this determinant in 9.4 x 106 and in 38 x 106 spleen cells from immunized and nonimmunized DBA/1 mice. The findings reported here indicate that the phenotypic expression of the genetic control(s) for immune responsiveness to different immunopotent regions of (Phe, G)-Pro--L is directly correlated with the number of immunocompetent response units detected in two inbred mouse strains. In the spleens of immunized F1 donors, similar frequencies of one limiting precursor in 3.0 x 106 and in 2.8 x 106 cells were detected for (Phe, G) and Pro--L, respectively. The results of a chi-square test for independence of (Phe, G) and Pro--L responses in F1 animals is compatible with the hypothesis that the transferred spleen cells limiting the response to (Phe, G)-Pro--L are restricted to generate antibodies specific for only one of the two determinants of this macromolecule.