Requirement for Continuous Antigenic Stimulation in the Development and Differentiation of Antibody-Forming Cells

Abstract

The levels of both antigen and specific immunoglobulin are considered important regulatory mechanisms which determine the size of the antibody-producing cell compartment. Uhr and Finkelstein (1) demonstrated that the presence of antigen is essential for continuous synthesis of 19S antibody at any stage after its initiation. Recent studies suggest that repeated antigen contact of immunocompetent cells is required for complete differentiation (2-4). The X-Y-Z immune cell maturation scheme of Sercarz and Coons (5) is established on this assumption.This concept of the continuous role of antigen in the immune response is consistent with the increasing body of evidence demonstrating that antigen does localize and persist in the lymphatic tissue during a primary response (6-9). One site in lymphatic tissue in which antigen has been demonstrated to be localized extracellularly is the germinal center (l(I-11). Although the functional significance of this antigen deposition is not completely resolved, experimental evidence demonstrates that there may be a causal relationship between the antigen localization and the presence and proliferation of the characteristic, large pyroninophilic cells of the germinal centers (8,12). These cells by morphologic and functional parameters are considered immunologically competent cells (13)(14)(15)(16)(17).We have further suggested that during the primary immune reaction the persistence of antigen in germinal centers is a dynamic process which is sensitive to and altered by the level of free specific antibody (18). Studies of Sahiar and Schwartz (19) showed that rabbits receiving heterologous passive antibody 1 hr after antigen had a marked decrease in germinal center hyperplasia during the primary response. Thus two parameters reflect antibody-mediated immune suppression, the decrease in the size of the 19S and 7S antibody-producing cell compartments (20) and decreased proliferation of pyroninophilic cells in germinal centers, this being reflected as lack of growth of the centers.

Characteristics of Immunological Memory in Mice

“…The early development of memory reported here agrees with the observations of other workers who have studied the 2 ° humoral or cellular responses to erythrocyte antigens (2,9,25,26). In contrast to these results is the length of time taken for memory to develop to some protein antigens (1,4).…”

“…Using these criteria, it has been demonstrated that priming for a 2 ° response to sheep erythrocytes (SRBC) in mice occurs during a 4-5 day period after immunization (2,3). For other antigens, the development of memory may be a longer process (1,4) and the long-term persistence of antigen may be an important requirement, as it may also be for the maintenance of memory (5).…”

“…For other antigens, the development of memory may be a longer process (1,4) and the long-term persistence of antigen may be an important requirement, as it may also be for the maintenance of memory (5). At a cellular level, preparation for a 2 ° response includes the generation of primed IgM and IgG AFC precursors (2,6), together with a helper T-lymphocyte population (7). The X-Y-Z scheme of immune cell maturation (8, 9) was devised to account for the relationships between unprimed lymphocytes, memory cells, and AFC.…”

“…On days 0 (30 rain), 1, 2, 3, 4, 5, 7, 10, or 15 after antigen, groups of these animals were treated with CP and anti-SRBC antibody. These agents were chosen to partially remove antigenic stimulus (2,19), and to kill, or halt division of, activated T and B lymphocytes (20,21). Control groups received either antigen (control 2 ° response) or immunosuppressants (control 1 ° response) alone.…”

Transition in the Character of Immunological Memory in Mice after Immunization

“…The immunological memory generated by intra venous immunization with alum-precipitated bovine serum albumin (AP-BSA) developed with time through the following threephases: (a) the early phase in which the memory forIgM antibody response (IgM memory) was generated within a few days after immunization, (b) the intermediate phase (from a few days up to about a month after immunization) in which IgG memory grew andIgM memory decreased, and (c) the late phase in which only IgG memory persisted but progressively degenerated (from than a month afterimmunization). Such a process may be applicable to the immunological memory for many other thymus-dependent antigens [2,8,27,31].…”