Antibody response of rabbit blood lymphocytes in vitro. Kinetics, clone size, and clonotype analysis in response to streptococcal group polysaccharide antigens.

Braun, Dietmar; Quintáns, José; Luzzati, Alma L.; Lefkovits, Ivan; Read, Stanley

doi:10.1084/jem.143.2.360

Cited by 23 publications

(26 citation statements)

References 17 publications

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“…It appears that with repeated immunizations individual animals respond with identical clonotypes, a phenomenon called persistence of clonotypes, with little to no change of the relative concentration of each clonotype. This is even reflected in the number of B-cell precursors circulating in the blood as memory cells and expressing defined clonotypes (7).…”

Section: B the Restricted Nature Of The Antibody Responsementioning

confidence: 99%

The Use of Streptococcal Antigens to Probe the Mechanisms of Immunity

Braun

1983

Microbiology and Immunology

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The difficulty to comprehend the immune response resides both in the complexity of antigens, in terms of linear structure and arrangement in space, as the eliciting signal and the complex molecular and cellular interactions that result in the induction and the expression of antibodies. In addition, every antibody response is the sum of many clonal responses, specific and cross-reactive. Hence, any study dealing with the expression of antibodies calls in the last analysis for means to separate the antibody forming clones and their products, the monoclonal antibodies (9). The analysis of myeloma proteins (37) as an alternative for antibodies with predetermined specificities can only be regarded as a substitute for the issue to be addressed -these substrates are the final products that rarely have known antigen specificity and cannot tell the story leading to their expression -until a unifying model will become available to resolve the structure-function relationship of antibodies, the connections between specific antibodies and correlating T cell receptor specificity, and the genetics of the immune response and of the antibody variable regions.A number of different antigen systems and of antibody models have been used to tackle these problems (18). Undoubtedly, the streptococcal group polysaccharide antigens have played a significant role in this line of research, since antibody responses of restricted heterogeneity to these bacterial cell wall antigens were reported (28,35), and could later be elicited at will and in a predictable fashion both in selectively bred rabbits and in certain inbred strains of mice (5,8, IS,29). No other antigen system has been applied for such a variety of studies until the monoclonal antibodies were generally made available by the hybridoma technique (25, 32).I t is the purpose of this review to point out the contributions made to immunology and to bacteriology by the system of antibodies of restricted heterogeneity This article was written on the basis of the special lecture delivered at the 56th Annual Meeting of Japanese Society for Bacteriology (Osaka, April 5-7, 1983). 823

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Section: B the Restricted Nature Of The Antibody Responsementioning

confidence: 99%

The Use of Streptococcal Antigens to Probe the Mechanisms of Immunity

Braun

1983

Microbiology and Immunology

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“…In the context of this work, maturation of immune responses refers to the emergence of antibodies with different subsite specificities to one antigen presumably from a pre-existing pool of B-cell precursors. Accordingly, clonal hierarchy established as memory in vivo, which in antibody responses of restricted heterogeneity is measurable in mg ml -~ of antiserum, persists in vitro under conditions where limiting numbers of lymphocytes were cultured, permitting an estimate of the frequency of responding units (27). These and additional results are evidence for the lack of maturation of anti-streptococcal group polysaccharide responses (48,49).…”

Section: Discussionmentioning

confidence: 60%

“…In competition experiments, a 20-fold excess of the nonhemolytic antibody K127-760II failed to inhibit the lyric action of antibody K151-748II in the spot test (27,33). Further, in the quantitative CdL assay (10, 50 and 75% lysis by antibody K151-748II), no inhibition of lysis was observed up to a 100-fold molar excess of the nonlytic antibody K127-760II, indicating that at these concentrations the low affinity antibody did not compete with the high affinity antibody.…”

Section: Functional Properties Of Low and High Affinity Antibodiesmentioning

confidence: 99%

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Distinct functions of monoclonal IgG antibody depend on antigen-site specificities.

Schalch¹,

Wright²,

Rodkey³

et al. 1979

The Journal of Experimental Medicine

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Intraveneous hyperimmunization of selectivity bred rabbits with streptococcal group A-variant vaccines elicits antibody responses of restricted heterogeneity at high antibody levels. All antisera contain two functionally distinct antibody populations, which can be isolated in single-band purity upon analytical isoelectric focusing. Typical examples of these two kinds of single-band antibodies were investigated in great detail for several parameters by a variety of methods. 85--99% of the streptococcal group A-variant polysaccharide (Av-CHO)-specific antibody in the antisera does not precipitate the isolated 5,000 daltons poly-L-rhamnose antigen, neither agglutinates nor lyses in the presence of complement Av-CHO-coated sheep erythrocytes (SRBC), binds the radio-labeled Av-CHO with an association constant in the ragne of 10(5)--10(6) M-1, and is of terminal specificity (nonreducing end) for the linear Av-CHO. In contrast, the minor fraction of Av-CHO-specific antibody (1--15%) does precipitate the linear Av-CHO, both agglutinates and lyses Av-CHO-coated SRBC in the presence of complement, has an affinity range of 10(8)--10(9) M-1, and is of internal specificity for the Av-CHO. The antigenic determinants of the Av-CHO for the antibodies are nonoverlapping, only one Fab of the low affinity antibody can be bound whereas four Fab of the high affinity antibody are accommodated. Hence, the determinant specificity explains the functional differences observed, for there is no indication of subclass differences. A mechanistic model of the A-variant carbohydrate presentation on the vaccine appears to account best for the unbalanced levels of low and high affinity antibody.

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“…This stimulation induces an early wave of proliferation (17, 18) followed by the appearance of polysaccharide-specific PFC (2,7,20). Stimulation requires the presence of vaccine in culture, i.e.…”

mentioning

confidence: 99%

T Cell Activation of Primed Rabbit Blood Lymphocytes by Antigen

Andersen¹,

Pawlita²,

Lefkovits³

et al. 1979

Pathobiology

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Activation of primed rabbit PBL by homologous antigen in the early proliferative phase (on days 3–5) mainly involves lymphocytes which neither secrete specific antibody nor contain immunoglobulin in their cell membrane. This stimulation is antigen-specific, and evidence is given that the major proportion of these cells are T lymphocytes. The B cells forming Av-CHO-specific PFC were studied by autoradiography on days 6 and 12 of culture. Since incorporation of radioactive thymidine was found in the majority of PFC, these cells are also in proliferation.

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Antibody response of rabbit blood lymphocytes in vitro. Kinetics, clone size, and clonotype analysis in response to streptococcal group polysaccharide antigens.

Cited by 23 publications

References 17 publications

The Use of Streptococcal Antigens to Probe the Mechanisms of Immunity

The Use of Streptococcal Antigens to Probe the Mechanisms of Immunity

Distinct functions of monoclonal IgG antibody depend on antigen-site specificities.

T Cell Activation of Primed Rabbit Blood Lymphocytes by Antigen

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