Induction of immunity and tolerance <i>in vitro</i> by hapten protein conjugates. II. Carrier independence of the response to dinitrophenylated polymerized flagellin

Feldmann, Marc

doi:10.1002/eji.1830020208

Cited by 72 publications

(52 citation statements)

References 42 publications

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“…Vilro.--Since D N P P O L immunizes B cells directly in the absence of helper cells (1,3,4), the m e c h a n i s m of binding of this antigen molecule to B cell receptors bears m u c h more relevance to the actual m e c h a n i s m of B cell i m m u n i z a t i o n than is the case with antigens whose a n t i b o d y responses require the participation of helper…”

Section: Inhibition Of the Anti-dnp Response To D N P Pol Inmentioning

confidence: 99%

Induction of Immunity and Tolerance in Vitro by Hapten Protein Conjugates

Feldmann

1972

The Journal of Experimental Medicine

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A critical stage in the induction of antibody responses is the interaction of antigen molecules with the surface receptors of immunocompetent cells. This interaction may result in either immunity, or its opposite, immune tolerance. The differences between the pattern of antigen binding to nonthymus-dependent lymphocytes (B cells) 1 in immunity and tolerance are not fully understood. Recently, attempts were made to study this problem in tissue culture, using dinitrophenylated polymeric flagellin (DNP POL) as antigen (1). The interaction of antigen molecules with cell membranes may be readily studied in dissociated lymphoid cell populations in vitro, where antigen concentrations are relatively uniform and catabolism negligible compared with tile situation in vivo (2). Furthermore, since tile response to DNP POL in vitro does not require the participation of either thymus-dependent lymphocytes (T cells) (1, 3) carrier-reactive cells, or macrophages (4, 5), only the pattern of reaction of DNP POL molecules with B cells determines the ensuing immunological events. It was found that the number of 2,4-dinitrophenyl (DNP) haptenic groups present per monomeric unit of the DNP POL molecule (i.e. the epitope density) dictated its capacity to induce either immunity or tolerance (1). Antigen molecules with few DNP groups immunized, but never induced tolerance, whereas highly conjugated DNP POL induced tolerance, but never immunity (1). Based on these observations, a mechanism of B celt signal discrimination between immunity and tolerance was proposed, based on the number

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Section: Inhibition Of the Anti-dnp Response To D N P Pol Inmentioning

confidence: 99%

Induction of Immunity and Tolerance in Vitro by Hapten Protein Conjugates

Feldmann

1972

The Journal of Experimental Medicine

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“…This was predicted from the structure of NIP-POL since T cell independence has also been shown for a wide range of antigens with a repetitive determinant strnctnre (Martin, 1969;Arm.stroiig, Diener and Shellam, 1969;Diener, O'Callaghan and Kraft, 1971;Fcldniann and Basten, 1971;Feldmann, 1972;Andersson and Blomgren, 1971;Mciller, 1970;Moller and Michael, 1971;Sjol>erg, 1972;lluiriphrey, Parrott and East, 1964;Da\ies, Carter, Leuchars, Wallis andDietrich, 1970: Howard, Christie, Courtena\, Lenchars andDavies. 1971;Miranda, 1972;Mitchell, Grumet and McDevitt, 1972).…”

Section: Secondary Immune Response Hij Nude Micementioning

confidence: 87%

“…This may be eoupled to POL as a carrier, since presentation in the form of a repetitive determinant should produce a response iudependent of accessory cells (Feldmann and Iiasten, 1971;Feldmann, 1972). The response to NIP can readil\ be monitored by a plaque haemolysis assay for AFC, using NIP attached to SRC (Strausbach, Sulica and Civol, 1970), and using anti-globulin serum to reveal the different antibody classes (Sterzl aud Riha, 1965;Dresser and Wortis, 1965;Weilcr, Melletz and Breuninger-Peck, 1965).…”

Section: Introductionmentioning

confidence: 99%

Antigen‐initiated B Lymphocyte Differentiation. Characterisation of the Primary and Secondary Immune Responses of Normal and Athymic Mice to the Hapten 4‐hydroxy‐3‐iodo‐5‐nitrophenylacetic Acid Presented on the Carrier Polymerised Bacterial Flagellin

Schlegel

1974

Aust J Exp Biol Med

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Summary The hapten 4‐hydroxy‐3‐iodo‐5‐nitrophenylacetic acid (NIP) has been coupled to polymerised bacterial flagellin (POL) to produce a linear array of repetitive antigenic determinants. The kinetics and nature of the immune response to this antigen have been studied in normal and athymic nude mice. The primary immune response by normal mice involved exclusively IgM antibody‐forming cells (AFC), whereas the response by normal mice primed to the NIP determinant consisted of IgG as well as IgM AFC. Both the primary and secondary IgM responses by nude mice were unimpaired, whereas the IgG response was absent, indicating that thymus derived (T) lymphocytes were not necessary for complete expression of the IgM response but were essential for the production of an IgG response. The kinetics of the primary IgM response in normal as well as nude mice were unusual, giving a peak at 3 rather than 4‐5 days and giving a cycling response after the initial decline. However, the kinetics of the IgM response in both normal and nude NIP‐primed mice were normal with a peak at 4‐5 days. This suggests that the primary response to NIP‐POL may be the characteristic response of true “virgin” AFC‐progenitors rather than the response of pre‐immunised AFC‐progenitors.

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“…In contrast, normal antibody production to DNP on a thymusindependent carrier, such as POL, can be demonstrated in the same culture system. Because unprimed cells from a T-containing spleen cell population, such as normal CBA spleen, do not produce significant responses in vitro to nonpolyrneric hapten-protein conjugates such as DNP F3'G, DNP KLH, or DNP monomeric flagellin (11,23), these antigenic systems (DNP F'yG and DNP KLH) offered a way of determining whether the allogeneic factor augmented immune induction or merely augmented the proliferation of B cells which have already been immunized. Thus the effect of ATCFvG or ATCKLH on the response of cells from nude spleen to various DNP conjugates was ascer- Each value represents the arithmetic mean of three to six cultures of 30 X 106 nude spleen cells which were cultured together with either SRC or DRC, DNP POL, and CG POL for 4 days.…”

Section: Effect Of the Allogeneic Reaction On The Response To Dnp Fq/mentioning

confidence: 99%

Cell Interactions in the Immune Response in Vitro

Feldmann

Basten

1972

The Journal of Experimental Medicine

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138

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Various theories have been proposed to explain the mechanism of collaboration between thymus-derived (T) 1 and nonthymus-derived (B) lymphocytes in the induction of antibody responses. Among these is the possibility that T cells activated by antigen secrete a soluble factor capable of facilitating the induction of antibody production by B cells. In a system involving allogeneic combinations of lymphoid cells, Dutton et al. (1) in vitro and Katz et al. (2) and Kreth and Williamson (3) in vivo have obtained evidence for the release by T cells of a nonspecific factor stimulating B cell responsiveness. In these experiments T cells were activated by histocompatibility antigens, whereas the response of B cells to other antigens, such as heterologous erythrocytes or hapten-protein conjugates, was assayed. The recent demonstration by Schimpl and Wecker (4) of the production by alloantigenically stimulated T cells of a factor which could partially replace T cell function in the sheep red cell response has provided more direct evidence for the existence of a nonspecific component in T cell helper activity.In contrast, Feldmann and Basten (5, 6) have found that T cells activated by a particular antigen elaborated a factor capable of triggering syngeneic B cells, but only

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Induction of immunity and tolerance in vitro by hapten protein conjugates. II. Carrier independence of the response to dinitrophenylated polymerized flagellin

Cited by 72 publications

References 42 publications

Induction of Immunity and Tolerance in Vitro by Hapten Protein Conjugates

Induction of Immunity and Tolerance in Vitro by Hapten Protein Conjugates

Antigen‐initiated B Lymphocyte Differentiation. Characterisation of the Primary and Secondary Immune Responses of Normal and Athymic Mice to the Hapten 4‐hydroxy‐3‐iodo‐5‐nitrophenylacetic Acid Presented on the Carrier Polymerised Bacterial Flagellin

Cell Interactions in the Immune Response in Vitro

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