Cellular Mechanisms of Adjuvant Action of Bacterial Lipopolysaccharide in Anti‐Sheep Red Blood Cell Antibody Response

A study was performed to clarify the roles of primary and secondary injections of antigen and adjuvant (capsular polysaccharide of Klebsiella pneumoniae, CPS-K) in induction of antibody responses and in development of immunological memory in mice to bovine serum albumin (BSA). A primary injecion of BSA alone neither induced significant primary antibody response nor increased immunological memory for a secondary antibody response but, if primary injections of BSA and CPS-K were performed simultaneously, high antibody responses were induced. Moreover, a prior injection of BSA alone or CPS-K alone decreased the level of primary antibody response and the degree of increase in memory following the subsequent injection of BSA mixed with CPS-K. In contrast, a secondary injection of BSA alone into mice once primed with a mixture of BSA and CPS-K elicited very high secondary type antibody response and increased secondarily the memory for a tertiary antibody response. Injection of CPS-K simultaneously with or shortly before or after the secondary injection of BSA did not increase the level of the secondary antibody response and the degree of the secondary increase in memory. Augmentation of the secondary antibody response was elicited by simultaneous injection of CPS-K only when the secondary response was induced inadequately by a suboptimum or supraoptimum dose of antigen.

Section: Discussionsupporting

confidence: 58%

Adjuvant Action of Capsular Polysaccharide of Klebsiella pneumoniae on Antibody Response

Nakashima

Kato

1975

“…As shown in Table 3, previous injections of LPS did not exert any priming effect on anti-SRBC PFC responses of mice to restimulation with either LPS or SRBC, and the restimulated mice showed direct and indirect PFC responses similar to those in mice primarily stimulated. It is well known that the secondary antibody response elicited by a second injection of the same antigen into animals previously primed with a given antigen is quite different from the primary antibody response in the following characteristics; a response with shortened induction period, heightened antibody titer and predominant 7S antibody or indirect PFC [20]. The present study demonstrated that restimulation of LPS-primed mice with LPS or SRBC did not cause any `secondary -type' antibody response.…”

Section: Cytokineticsmentioning

confidence: 53%

“…For example, injections of LPS into mice in conjunction with xenogeneic erythrocytes as the antigen result in marked increases in the numbers of anti-erythrocyte antibody plaqueforming cells (PFC) to be generated in the spleens [20,21]. Furthermore, even without the administration of any erythrocyte antigen, an injection of LPS alone nonspecifically increases the number of PFC to xenogeneic erythrocytes in the mouse spleens [7,9].…”

mentioning

confidence: 99%

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

Nakano

Uchiyama

Tanabe

et al. 1975

Self Cite

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.

“…Bacterial lipopolysaccharide (LPS) extracted from gram-negative bacteria enhances the antibody response to certain antigens [2,9,17,19,21], while under some experimental conditions, LPS is known to have reverse potency as an immunosuppressant [21]. Injection of LPS several days prior to immunization was shown to suppress antibody formation against the antigen at the serum level [4] and at the antibody-producing cell level in the spleen [17].…”

mentioning

confidence: 99%

“…Injection of LPS several days prior to immunization was shown to suppress antibody formation against the antigen at the serum level [4] and at the antibody-producing cell level in the spleen [17].…”

mentioning

confidence: 99%

Immunosuppressive Effect of Bacterial Lipopolysaccharide on Antibody Response

Nakano

Tanabe

Saito

et al. 1976

Self Cite

Injection of endotoxins (bacterial lipopolysaccharide: LPS) several days prior to immunization causes the suppression of antibody response. The suppressive effects of several kinds of LPS preparations on the plaque-forming cell (PFC) antibody response in the spleen of mice were examined after immunization with sheep red blood cells (SRBC). Glycolipids obtained from heptoseless mutants (Re form) of salmonella or its lipid A preparation coupled artificially with bovine serum albumin (BSA) are capable, like LPS obtained from a wild type (S form) strain, of inducing suppression of the PFC response, while alkaline-detoxified LPS can not. The refractory periods of the PFC response induced by LPS injection last only a few days. However, the use of cyclophosphamide (CY) together with LPS can extend the refractory periods of antigenic stimulation for several weeks. Injections of LPS and CY can also induce unresponsive states of OH agglutinin antibody response to antigenic stimulation with formalin-killed organisms of Escherichia coli or Salmonella enteritidis (presumably both thymusindependent antigens). These unresponsive states induced by LPS and CY are easily terminated by a transfer of syngeneic bone marrow cells but not by thymocyte transfer.