IgG response <i>in vitro</i>. I. The requirement for an intermediate responsive cell type

North, John R.; Askonas, Brigitte A.

doi:10.1002/eji.1830060104

Cited by 28 publications

(9 citation statements)

References 34 publications

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“…Several subpopulations of sensitised B cells, in addition to AFC's and memory B cells, have now been identified. One of these subpopulations is an intermediate B memory cell type which has partly developed towards a mature AFC (North and Askonas, 1976). This intermediate type of B cell has been shown to be associated with the anamnestic antibody response that is seen after short term m vitro culture, while a longer culture period is required for the anamnestic antibody response produced by the 'true' B memory cell (North and Maizels, 1977).…”

Section: Discussionmentioning

confidence: 99%

BABESIA MICROTI IN MICE. SUBPOPULATIONS OF CELLS INVOLVED IN THE ADOPTIVE TRANSFER OF IMMUNITY WITH IMMUNE SPLEEN CELLS

Meeusen

Lloyd

Soulsby

1984

Aust J Exp Biol Med

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Summary Protection against a primary Babesia microti infection in mice, induced by the adoptive transfer of immune spleen cells, was abolished when the immune spleen cells were treated with mitomycin C prior to transfer. Since mitomycin C treatment prevents the replication of lymphocytes without affecting other cell functions, these results would suggest that the transferred cells required proliferation in the recipient mice before they could exert their protective effect, and this excludes the already differentiated antibody‐forming cells (AFC's), macrophages and sensitised helper T cells. This was partly supported by the finding that Sephadex G‐10 non‐adherent immune cells, depleted of macrophages and AFC's, still conferred a strong protection after transfer. However, the Sephadex G‐10 adherent cells, on a cell to cell basis, initially conferred a better protection against B. microti than did the non‐adherent cells or unfractionated immune spleen cells. The possibility of the retention of an intermediate B memory cell type on the Sephadex G‐10 columns and the suppression of antibody production are discussed in view of these results.

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Section: Discussionmentioning

confidence: 99%

BABESIA MICROTI IN MICE. SUBPOPULATIONS OF CELLS INVOLVED IN THE ADOPTIVE TRANSFER OF IMMUNITY WITH IMMUNE SPLEEN CELLS

Meeusen

Lloyd

Soulsby

1984

Aust J Exp Biol Med

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“…Recently, North and Askonas have described an in vitro system (24) in which very high responses to DNPKLH can be obtained. Just as in the anamnestic response in vivo, the vast majority of anti-DNP-PFC induced in these cultures produce IgG antibodies, whereas IgM-PFC represent only 10-15% of the response.…”

Section: Resultsmentioning

confidence: 99%

“…As the IgG response is known to be even more sensitive to the removal of T cells than is the primary, predominantly IgM response (25), we have used this system for a study on the production and action of TRF in the response to soluble protein antigens. The same immunization schedule was used as described by North and Askonas (24), and tissue cultures were set up as described in Materials and Methods. To characterize this response as a classical carrier-hapten system, it was investigated if the recognition of the DNP moiety by the B cells could be blocked by free hapten and if, on the other side, the recognition of the KLH moiety by helper T cells could be blocked by free carrier.…”

Section: Resultsmentioning

confidence: 99%

“…There are, however, no reports demonstrating the actual involvement of TRF in the in vitro immune response of entire mouse spleen cell populations. Carrier-hapten systems as the ones employed in this report (24) are well suited to study this question, because it is possible to stimulate the carrier-specific cells by unhaptenated carrier without stimulating the hapten-reactive B cells. Hapten-free homologous carrier or heterologous carrier-hapten conjugates have been used by several authors (26)(27)(28)(29)(30) in attempts to analyze selectively the reactivity of helper T cells and hapten-specific B cells.…”

Section: Resultsmentioning

confidence: 99%

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Mechanism of T-cell help in the immune response to soluble protein antigens. I. Evidence for in situ generation and action of T-cell-replacing factor during the anamnestic response to dinitrophenyl keyhole limpet hemocyanin in vitro.

Schimpl¹,

Wecker²,

Hünig³

1977

The Journal of Experimental Medicine

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In the humoral immune response to most antigens studied so far, the presence of helper T cells is required for the generation of antibody-forming cells from precursor B cells. In terms of the classical carrier-hapten systems described by Mitchison (1), B cells specific for a hapten can only become antibody-forming cells if helper T cells react with antigenic determinants on the carrier molecule that the hapten is linked to. This finding has later on led to the hypothesis that the close proximity brought about by an antigen "bridge" between B cell and T cell is the prerequisite for T-B cooperation (2). Under this assumption, several concepts have been developed to explain the nature of T-cell help itself. Among these are: the focussing of antigen by the T cell onto the B cell (2, 3), a membrane interaction between the two cells (4), and the production of mediators, antigen specific (5-7) or nonspecific (4,(7)(8)(9)(10)(11)(12)(13)(14), by the antigen-stimulated T cell. In vitro studies have shown that T-cell-replacing factor (TRF),I a nonantigen-specific mediator produced by activated T cells (15), can replace T cells in primary and secondary immune responses to heterologous erythrocytes (15, 16). The action of TRF and similar factors described by other authors (4, 7-14) has so far been demonstrated by restoring the immune response to heterologous erythrocytes in T-cell-deprived cultures by addition of preparations containing the factor. On the other hand, the experiments reported by Hartmann (17) have shown that T cells activated to erythrocyte antigens in vivo do, upon antigenic challenge in vitro, not only restore the response of B-cell cultures to the epitopes of the same erythrocytes, but also to those of erythrocytes from another species added simultaneously to the same cultures. Although this co-stimulation is best explained by the in situ generation and action of TRF, the function, and indeed the presence of this mediator in complete spleen cell cultures during the immune response remains to be demonstrated.In order to study this question under the most stringent conditions, we chose the anamnestic IgG reaction to soluble carrier-hapten conjugates in vitro. The pronounced T-cell dependence of the IgG response to such a conjugate and the possibility to stimulate T and B cells separately with carrier and hapten determinants make it possible to investigate the action of TRF in the immune response to soluble protein antigens.

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“…If antibody formation in vivo or in vitro stops after elimination of most of the antigen, it is rapidly restored after renewed addition of the antigen. North and Askonas (10) conclude that it is "memory" in the form of precursor cells rather than autonomous antibody production that is transferred through many generations. While the term "memory cell" is usually applied to those cells that had been exposed to prior stimulation by the antigen, the terms antigen-sensitive cell or antigen-reactive cell have been used for cells that had no earlier contact with the antigen and yet bind a definite type of antigen.…”

mentioning

confidence: 99%

Mechanism of antigen-induced antibody biosynthesis from antibody precursors, the heavy and light immunoglobulin chains

Haurowitz¹

1978

Proc. Natl. Acad. Sci. U.S.A.

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The immediate precursors of antibody molecules, the heavy (H) and light (L) peptide chains of the immunoglobulins, combine with each other by means of disulfide bonds formed by dehydrogenation of their cysteine residues. In the absence of an antigen this process yields the heterogeneous mixture of normal immunoglobulins. Antigens or their processed derivatives (Ag) interfere with this stochastic process by noncovalent combination with complementarily fitting H chains. The (Ag.H). complexes thus formed, owing to the loss of rotational and translational freedom, combine preferentially with those L chains whose VL regions have some affinity for the determinants of the antigen molecule. Subsequent release of Ag from the (AgH'L). complexes yields free antigen and antibody molecules. Each of the released Ag molecules can be used repeatedly for the same reaction cycle and thus can induce the biosynthesis of a large number of antibody molecules. Any macromolecule, natural or synthetic, that has at least a few polar groups and that can penetrate to the nascent H and L chains can thus act as an antigen. Whereas the structure of the H and L chains is genetically determined and transmitted through the germ. line, the process induced by the antigen is a phenotypic phenomenon. The antigen acts in this process as a stereospecific cofactor or regulator of the thiol-disuilfide transhydrogenation of the combining H and L chains of immunoglobulins.

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IgG response in vitro. I. The requirement for an intermediate responsive cell type

Cited by 28 publications

References 34 publications

BABESIA MICROTI IN MICE. SUBPOPULATIONS OF CELLS INVOLVED IN THE ADOPTIVE TRANSFER OF IMMUNITY WITH IMMUNE SPLEEN CELLS

BABESIA MICROTI IN MICE. SUBPOPULATIONS OF CELLS INVOLVED IN THE ADOPTIVE TRANSFER OF IMMUNITY WITH IMMUNE SPLEEN CELLS

Mechanism of T-cell help in the immune response to soluble protein antigens. I. Evidence for in situ generation and action of T-cell-replacing factor during the anamnestic response to dinitrophenyl keyhole limpet hemocyanin in vitro.

Mechanism of antigen-induced antibody biosynthesis from antibody precursors, the heavy and light immunoglobulin chains

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