Facilitation of immune hemolysis by an interaction between red cell-sensitizing antibody and gamma-globulin allotype antibody.

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.

Section: Discussionmentioning

confidence: 99%

Cells Involved in the Immune Response

Richter

Abdou

1969

“…Apparently, imrnunocytes are differentiated so as to synthesize exclusively antibody of one given antigen-specifidty (1-10), biological activity (11,12), and immunoglobulin class or subclass (4,(12)(13)(14)(15). Specialization of imrnunocytes is so extreme that only one allotypic variant of a particular immunoglobulin subclass is produced by cells possessing the genetic information for two variants (16)(17)(18). Identification of the source of the diversity among irnrnunocytes is a major goal in immunology, since it bears upon the instructive and selective theories of antibody formation.…”

mentioning

confidence: 99%

Cellular Differentiation of the Immune System of Mice

Shearer

Cudkowicz

Priore

1969

Antibody-forming cells produce, as a rule, only one of several possible species of immunoglobulins at any one time. Apparently, imrnunocytes are differentiated so as to synthesize exclusively antibody of one given antigen-specifidty (1-10), biological activity (11, 12), and immunoglobulin class or subclass (4,(12)(13)(14)(15). Specialization of imrnunocytes is so extreme that only one allotypic variant of a particular immunoglobulin subclass is produced by cells possessing the genetic information for two variants (16-18). Identification of the source of the diversity among irnrnunocytes is a major goal in immunology, since it bears upon the instructive and selective theories of antibody formation. One way of studying the mechanism by which this diversity is generated, is to recognize the stages and cell types along the lymphoid and/or myeloid differentiation pathways at which specialized functions arise, and possibly, the sequential development of different levels of specialization.The immediate precursors of antibody-forming cells are units d one or more highly integrated cell types that do not release antibody, but interact with antigen and generate functional immunocytes by proliferation and/or differentiation (2, 3, 12, 19). Such integrated units, called antigen-sensitive units (ASU), are found in spleen, lymph nodes (19,20), and peripheral blood (unpublished results), and are detected by transplantation methods. Some of the cellular components of ASU are found separately in marrow and in thymus, since artificial mixtures of ceils from these and other organs yield functional ASU (21, 22). Like antibody-forming cells, splenic ASU have undergone antigen-specificity differentiation (8,9,23,24), antibody-class differentiation (12) and presumably allotypic restriction (18) before contact with antigen. Hence, diversity had occurred at least at the time of splenic ASU assembly. In a preceeding paper of this series (12) we demonstrated that splenic ASU reacting with the antigen complex of sheep erythrocytes were specialized, for they generated either hemolytic plaque-forming cells (PFC) or hemagglutinating duster-forming cells (CFC), but not both. Furthermore, some of the precursors of hemolysin-forming cells generated directl

“…The indirect hemolytic plaque test detecting 7S-producing cells (14)(15)(16) was carried out according to Dresser and Wortis (15). A high degree of inhibition of 19S plaques was found when using our unabsorbed rabbit-anti-mouse 7S antiserum confirming the findings of others (15).…”

mentioning

confidence: 99%

Antibody Synthesis at the Cellular Level

Wigzell

1966

Specific inhibition of the humoral component of the immune response by passively administered antibody has been demonstrated in a variety of experimental systems indicating the important role of antibody as a feedback factor during immune response (1-8, and earlier references quoted in reference 1). Both 19S and 7S antibodies have been found to function as inhibitors, 7S as a rule being more efficient than 19S antibodies (6-8). Passively transferred antibody has been found particularly efficient as an inhibitor if administered prior to or during the induction of both 19S and 7S antibody synthesis, whereas an already producing 7S system has been considered more resistant to inhibition than a comparable 19S system (6-8). This difference between the two antibody systems is in agreement with findings t h a t 7S synthesis in most systems is very long-lived compared to 19S production indicating either that the 7S-producing system is not as easily depleted of antigen as is the 19S system or the 7S synthesizing cells are very long-lived even in complete absence of antigen 9-12).In the present article the concept of the difference between 19S-and 7S-synthesizing systems with regard to sensitivity to antibody-induced suppression has been challenged. Precise studies of 19S and 7S antibody synthesis at a given moment are now possible at the cellular level using the direct (13) and indirect (14--16) hemolytic plaque tests. Using these techniques, particular attention has been focused on the effect of giving antibody well after the primary peaks of 19S and 7S synthesis. Material and MetkodsAnimals.--Mice of the following inbred strains were used: A/SnK1, A.BY/KI, A.SW/K1, CBA/KI, C3H/K1, and C57BL/K1. Some experiments were performed using Fl-hybrids of two of these strains. The mice were between 2 and 5 months of age when used. Within each experiment all mice were of the same strain, sex, and age.Angbodies.--Antibodies for inhibition were produced by repeated intraperitoneal injections of 4 X 108 sheep or chicken red blood cells (SRBC or ChRBC) into groups of 40 to 100 mice. The animals received on the average five to twelve 2-wk injections and were bled 5 to 10 days after the last one. Care was taken to ensure that the animals were immunized at least once against the same batch of erythrocytes that was used in the inhibition experiment(s) for induction of the primary response. The antisera for inhibition were produced and used within the same strain. 953on May 7, 2018 jem.rupress.org Downloaded from