Relationship of Germinal Centers in Lymphoid Tissue to Immunological Memory

Abstract

Transfer of adoptive immunity has proved useful in detection and characterization of the ceils carrying immunological memory. By introducing varying time intervals between transfer and reexposure to antigen in the recipients, the duration of responsiveness of memory cells was defined. Perkins and Makinodan (1) showed that, with donor ceils taken 4--6 wk after sensitization, little change in responsiveness of the primed cells occurs over the first few days following transfer. The results of Dresser (2) and Celada (3), however, indicate that when challenge with antigen is delayed for a month or longer after transfer there is a progressive decay in the responsiveness of the transferred cells. Indeed, Celada has shown a biphasic dedine of memory upon transfer of sensitized cells, which he interpreted to be due to two populations of memory cells, having half-lives of 26 and 190 days, respectively.The importance of nondividing or slowly proliferating cells in the maintenance of long-term immunity to certain antigens has been illustrated in a number of test systems. Lack of incorporation of thymidine-*H by primed cells transferred at short intervals after challenge with antigen in vivo, led Cohen and Talmage (4) to condude that the memory cell was not part of a rapidly dividing cell population. This condusion is compatible with the more recent findings of Gowans and Uhr (5) that long-term memory for the immune response to $X174 can be transferred by thoracic duct cells consisting almost entirely of small lymphocytes. X-irradiation studies have also suggested that nonreplicating cells are involved in long-term immunological memory (6-8). Moreover, long-lived small lymphocytes from peripheral blood of sensitized individuals have been identified as the cell type capable of transforming into blasts upon reexposure to antigen (9).The precursors of these nondividing cells which must be present during the early stages of the development of immunological memory, and the stimuli needed for such precursors to differentiate into small lymphocytes, are of particular theoretical *

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

“…In terms of formation of sensitized cells, the marked depression of the 7S memory after passive immunization at 24 hr (in contrast to the enhancement of 19S memory) corresponds to the suppressed growth of germinal centers during the primary response. Thus, if the germinal center is, as has been suggested, a site of the proliferative expansion of immunocompetent cells (17,12), these data indicate that the germinal center growth is related to the 7S cellular response. The functional significance of persisting antigen in these centers appears to be more closely related to the 7S antibody response and the development of 7S memory.…”

“…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.…”

“…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).…”

Localization of Immunological Complexes Fixing Ss1c (C3) in Germinal Centers of Lymph Nodes

“…Evidence has also been presented that germinal centers are linked in some way to the enhanced antibody synthesis associated with immunological memory (27,76,77). Immunological memory, as usually defined, is known to be associated with synthesis of IgG molecules (27).…”

“…These dendritic processes in turn are in intimate contact with lymphocytes and blastoid ceils (52). The lymphocytes in germinal centers, many of which are actively replicaring cells, have been regarded as precursors of plasma cells (21,(34)(35)(36)(37)80), or possible "memory cells" (12,73,76,77).Other authors have described the presence and production of immunoglobulins and antibodies in germinal centers (8,15,16,45,49,59,80,81). However, Pernis has submitted evidence that at least some of the immunoglobullns present in germinal centers are not synthesized locally (61).Germinal centers have been associated with antibody and immunoglobulin production in other ways.…”