The Use of Bacterial Lipopolysaccharides to Show That Two Signals Are Required for the Induction of Antibody Synthesis

Watson, James D.; Trenkner, Ekkhart; Cohn, Melvin

doi:10.1084/jem.138.3.699

Cited by 120 publications

(76 citation statements)

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“…The mechanism by which the observed antibody response occurred would seem to be best explained by the ability of LPS to bypass the normal T-cell helper function. Such an effect in the antibody production to T-dependent antigens has been previously demonstrated both in vivo or in vitro with antigens such as heterologous erythrocytes (6)(7)(8), haptens (9,10), and with the antigen used in the present studies, namely HGG (11). In this regard, perhaps the most convincing data is that obtained by Watson et al (10), who showed that the spleens of congenitally athymic mice (B cells only) could be induced to form antibody in vitro to a hapten free of any carrier molecule when the culture was supplemented with LPS.…”

Section: Discussionmentioning

confidence: 99%

The Ability of Bacterial Lipopolysaccharide to Modulate the Induction of Unresponsiveness to a State of Immunity

Louis

Chiller

Weigle

1973

The Journal of Experimental Medicine

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There exists a body of evidence which details that the antibody response to a number of different antigens requires the cooperation between thymus-derived lymphocytes (T cells) and bone marrow-derived lymphocytes (B cells) in a reaction whose net effect is the production of specific antibody by B cells (1). Both of these lymphocyte classes can be made specifically unresponsive to a given antigen (2), although each specific population displays a distinct kinetic pattern in the induction and maintenance of unresponsiveness (3).Bacterial lipopolysaccharides (LPS) 1 are mitogenic for B lymphocytes (4, 5), a phenomenon which may be related to their ability to circumvent the requirement of T cells for antibody formation to antigens which normally require cellular cooperation. The latter has been demonstrated both in vivo or in vitro using such T celldependent antigens as sheep erythrocytes (6-8), haptens (9, 10), and serum proteins (11). LPS can also prevent immunological unresponsiveness. This effect was originally described by Claman (12), who observed that mice which were given LPS after a normally tolerogenic dose of bovine gamma globulin (BGG) did not become tolerant. Golub and Weigle (13) subsequently defined the temporal relationship between the injection of tolerogen and LPS and furthermore demonstrated that the effect of LPS on the induction of tolerance was independent of its activity on the phagocytic index of the reticuloendothelial system.

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Section: Discussionmentioning

confidence: 99%

The Ability of Bacterial Lipopolysaccharide to Modulate the Induction of Unresponsiveness to a State of Immunity

Louis

Chiller

Weigle

1973

The Journal of Experimental Medicine

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“…The mechanisms as the cellular level have been investigated extensively but are not yet clear. The enhancing effect (adjuvant effect) of LPS has been thought to be caused by direct activation of B cells by LPS; LPS induces DNA synthesis (15) and polyclonal antibody production by B cells (15,17), and it enhances specific antibody response in circumstances where effects of helper T cells are absent or limited (16,20,28). LPS also prevents induction of immunological tolerance in B cells (12).…”

mentioning

confidence: 99%

“…Its action on antibody response is diphasic, being either enhancing (1, 4,5,14,16,20,21,25,27,28) or suppressive (24). The immune system involving antibody response is composed of several different cell populations (9): B cells, T cells and macrophages.…”

mentioning

confidence: 99%

“…LPS also prevents induction of immunological tolerance in B cells (12). On the basis of these effects of LPS on B cell responses, some investigators (12,28) have postulated that LPS acts directly on B cells as a second signal in the framework of a two-signal model of immunity (2). However, this interpretation should be reconsidered in view of reports showing that T cells or macrophages are involved as essential cellular elements in the adjuvant effect of LPS.…”

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Modulation of Immune Response by Bacterial Lipopolysaccharide (LPS): Roles of Macrophages and T Cells in In Vitro Adjuvant Effect of LPS on Antibody Response to T Cell‐Dependent and T Cell‐Independent Antigens

Uchiyama

1982

Microbiology and Immunology

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The roles of macrophages and T cells in the adjuvant effect of lipopolysaccharide (LPS) were studied. In vitro anti-trinitrophenyl (anti-TNP) antibody responses to TNP-Ficoll and TNP-keyhole limpet hemocyanine (TNP-KLH) in spleen cells of C57BL/6 mice showed the most enhancement, when LPS was added to cultures at I fI.g/ml 48 hr after culture was started. The responses to these antigens were enhanced markedly by LPS in whole and macrophage-depleted spleen cells. The enhancement was greater in the latter group than in the former. The adjuvant effect among whole, T cell-depleted, macrophage-depleted and both macrophage-and T cell-depleted spleen cells was compared. The response to TNP-Ficoll was enhanced markedly by LPS in all groups. The enhancement was greater in the latter two groups than in the first two groups. The response to TNP-KLH was enhanced by LPS strongly in macrophage-depleted spleen cells, moderately in whole and both macrophage-and T cell-depleted spleen cells, and only slightly in T cell-depleted spleen cells. Enhancement was restored to T celldepleted spleen cells by adding T cells. The response to TNP-KLH of macrophage-depleted spleen cells of LPS-responsive C3H/HeN mice which was enhanced by LPS was suppressed by adding splenic macrophages of C3H/HeN mice, but not of LPS-nonresponsive C3H/He] mice. The response to TNP-KLH of macrophage-depleted spleen cells of C3H/He] mice was not enhanced by LPS, irrespective of the addition of macrophages of C3H/HeN mice. The results indicate that B cells are activated directly by LPS, and T cells enhance and macrophages suppress the adjuvant effect of LPS.Lipopolysaccharide (LPS), a cell-wall component of Gram-negative bacilli, modulates antibody response. Its action on antibody response is diphasic, being either enhancing (1,4,5,14, 16,20,21,25,27,28) or suppressive (24). The immune system involving antibody response is composed of several different cell populations (9): B cells, T cells and macrophages. The modulatory effect of LPS 213

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“…Secondly, they show the adjuvant effect, enhancing antibody response to a variety of antigens when administered appropriately [19,25]. Thirdly, they convert tolerogenic or non-immunogenic signals into immunogenic ones [7,16,22,26,28,32] and fourthly, they possess mitogenic activity in transforming bone marrow-derived (B) cells but not T cells [3,27]. Although correlation be- of anti-HGG in response to aggregated HGG alone and upon subsequent injection of LPS they produced higher levels of antibodies but the degrees of increase in serum antibody levels were less than those in C57BL/6 mice ( Fig.…”

mentioning

confidence: 99%

Strain Differences in the Immunogenicity of Aggregated Human IgG and the Adjuvant Action of Lipopolysaccharide on the Low‐Responder Strain of Mice

Fujiwara

Yoshizaki

et al. 1976

Japanese Journal of Microbiology

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Strain differences in the antibody response to human IgG (HGG) were observed when aggregated HGG was injected intravenously. Lipopolysaccharide (LPS) administered subsequently markedly enhanced the antibody response to HGG in low responder C57BL/6 mice as compared with that in high responder DDD, C3H/He or (C57BL/6 × DDD)F1 mice. Aggregate‐free preparation of HGG at a dose of 0.5 mg induced immunological tolerance in all strains of mice tested. LPS injected subsequently converted tolerogenic, aggregate‐free HGG into immunogen in DDD mice but not in C57BL/6 mice. To determine the correlation between adjuvanticity and mitogenicity of LPS, spleen cells from normal mice were cultured in the presence of LPS and 3H‐thymidine uptake was measured. Spleen cells of DDD mice incorporated three times as much 3H‐thymidine as those of C57BL/6 mice. There seems no strong correlation between both activities of LPS. The data obtained are discussed in terms of strain differences in the macrophage function for processing the antigen.

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The Use of Bacterial Lipopolysaccharides to Show That Two Signals Are Required for the Induction of Antibody Synthesis

Cited by 120 publications

References 30 publications

The Ability of Bacterial Lipopolysaccharide to Modulate the Induction of Unresponsiveness to a State of Immunity

The Ability of Bacterial Lipopolysaccharide to Modulate the Induction of Unresponsiveness to a State of Immunity

Modulation of Immune Response by Bacterial Lipopolysaccharide (LPS): Roles of Macrophages and T Cells in In Vitro Adjuvant Effect of LPS on Antibody Response to T Cell‐Dependent and T Cell‐Independent Antigens

Strain Differences in the Immunogenicity of Aggregated Human IgG and the Adjuvant Action of Lipopolysaccharide on the Low‐Responder Strain of Mice

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