Nonspecific Elicitation of Antibody‐Forming Cells in the Mouse Spleen by Bacterial Lipopolysaccharide

Abstract

Mechanisms of nonspecific elicitation of anti-sheep erythrocyte (SRBC) hemolytic antibody plaqueforming cells (PFC) in mouse spleens with an injection of bacterial endotoxin (lipopolysaccharide (LPS)) were studied in comparison with the genesis of naturally occurring 'background' PFC in normal mouse spleens and of rapidly arising PFC in mouse spleens after immunization with SRBC. The cytokinetic pattern of anti-SRBC PFC response after an injection of LPS was quite different from that of the response elicited after immunization with SRBC. In addition, even though LPS nonspecifically elicited anti-SRBC PFC response in mice, LPS could not confer any immunological memory on mouse immunocytes for a 'secondary-type' anti-SRBC PFC response to restimulation with LPS or SRBC. The administration of rabbit anti-mouse thymocyte immunoglobulin or anti-SRBC antiserum in mice markedly suppressed the PFC response after immunization with SRBC, but did not do so after stimulation with LPS. Neonatally thymectomized mice could still respond to stimulation with LPS, producing anti-SRBC PFC in their spleens. Injections of actinomycin D or cyclophosphamide into mice resulted in obvious reductions of the PFC responses elicited by either LPS or SRBC. However, injections of these immunosuppressive antisera or drugs did not affect the number of anti-SRBC PFC in normal mouse spleens. These results suggest that the geneses of anti-SRBC PFC developed under different conditions, i.e., background PFC, LPS-stimulated PFC, and antigen-stimulated PFC, are quite different from each other, and that the nonspecific elicitation of anti-SRBC PFC by LPS does not require the helper function of T lymphocytes. No obvious difference, however, was observed in the time of ontogenic maturation among these three different anti-SRBC PFC in the mouse spleens judging from when they were first manifested after birth.

Characterization of Background Anti‐Trinitrophenyl Plaque‐Forming Cells Observed in Several Strains of Mice

“…This report suggests that natural antibodies are elicited by the immune response to antigenic substances brought by infections or diets. On the other hand, it was reported that background PFC to SRBC were detected in neonatally thymectomized mice [7,11] and in germ-free mice which were reared on chemically defined water-soluble diets [18]. These findings and our present studies suggest that background anti-TNP PFC are elicited by the natural maturation of precursor cells.…”

“…Each PFC value is a mean of several samples which were harvested from the indicated number of spleens. First day, one sample (4 mice) ; second day, 3 samples which had adjuvant activities and increased the number of PFC nonspecifically [11], could serve as stimulators of background PFC, the number of anti-TNP PFC was determined in germ-free ICR mice ( Table 6). The total lymphoid cell number in spleens was larger in conventional ICR mice (2.43 x 108 cells) than in germ-free ICR mice (1.5 x 108 cells), but the number of anti-TNP PFC per 106 cells was very similar in both groups (63.8/106 cells in germ-free mice and 78.5/106 cells in conventional mice.)…”

Immunosuppressive Effect of Bacterial Lipopolysaccharide on Antibody Response

“…Conversely, it may be determined from the time relation between LPS-and antigeninjection whether the immune responses are enhanced or suppressed after injection of LPS. LPS is capable of initiating nonspecifically the maturation of antibody-producing cell precursors (APCP) and converting them to antibody-producing cells (APC) [20]. The appearance of LPS-induced APC in the spleen of mice starts on day 1, becomes maximum on day 3 and lasts for about 1 week after the LPS stimulation [20].…”

“…LPS is capable of initiating nonspecifically the maturation of antibody-producing cell precursors (APCP) and converting them to antibody-producing cells (APC) [20]. The appearance of LPS-induced APC in the spleen of mice starts on day 1, becomes maximum on day 3 and lasts for about 1 week after the LPS stimulation [20]. Such nonspecific or polyclonal maturation of APCP induced by LPS may bring about a temporary exhaustion of APCP in the spleen which is followed by a refractory period of antibody responses against subsequent stimulation with antigens.…”

Further Studies of the Polysaccharide of Klebsiella pneumoniae Possessing Strong Adjuvanticity: III. Augmentation of the Antibody Response to Subcutaneously Injected Sheep Red Blood Cells by the Adjuvant Polysaccharide

“…This type of polyclonal activation of B cells first demonstrated in the present study has been characterized as developing at a late stage of stimulation exactly parallel in the time course with the development of the adjuvant action, and as including both IgM and IgG synthesis. It is well known that LPS (3,10,16) and DS (6, 7) activate B cells polyclonally both in vivo (10,16) and in vitro (3,6,7), but the activation in vivo is transient in general (10,16) and the activation of IgM synthesis is predominant (3,4), although significant activation of IgG synthesis by LPS has also been demonstrated in some in vitro (I, 2, 31) and in vivo (12) systems. One should however remember that IgM synthesis but not IgG synthesis which was induced by injection of K03 alone accompanied the corresponding increase in anti-SRBC PFC.…”