The Inheritance of Individual Antigenic Specificities of Rabbit Antibodies to Streptococcal Carbohydrates

Eichmann, Klaus; Kindt, Thomas J.

doi:10.1084/jem.134.2.532

Cited by 136 publications

(57 citation statements)

References 33 publications

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“…This association was observed regardless of strain or antibody titer and occurred throughout a primary and secondary response. This contrasts with other systems, including that defined with the mouse antisera in the present work, in which intra-and interstrain variabilities in expression of an idiotype are usual (18)(19)(20)(21)(22)(23). KShler has recent evidence in the in vitro primary anti-PC response which supports the findings presented here.…”

Section: Extent Of Shared Idiotypy On Hopc 8 and Mouse Anti-pc Antibocontrasting

confidence: 55%

“…5 The fact that the H88 idiotype is present on anti-PC antibodies of all mice, and thus can be considered a species-specific idiotype, clearly distinguishes the immune response to PC from other antibody responses. In systems such as the antistreptococcal and anti-p-azohapten antibody response idiotypic cross reactions are not usually observed except among selectively bred rabbits (18,22,24) or within an inbred strain of mice (20,21,23,25). Nisonoff and colleagues (21), however, have described strong idiotypic cross-reactions among anti-pazobenzoate antibodies from BALB/c, A, and C57BL/6 mice, though the relationship of these idiotypes to combining sites was not discussed.…”

Section: Extent Of Shared Idiotypy On Hopc 8 and Mouse Anti-pc Antibomentioning

confidence: 99%

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Clonal Nature of the Immune Response to Phosphorylcholine

Claflin

Davie

1974

The Journal of Experimental Medicine

102

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Studies of the binding characteristics for a number of choline analogues have revealed that antiphosphorylcholine (PC) 1 antibodies from 15 different inbred mouse strains which differ in histocompatibility and heavy-chain allotype are remarkably restricted and show the same binding specificity as a PC-binding myeloma protein, HOPC 8. 2' 3 This suggests that the anti-PC antibodies of all mice possess similar binding sites for PC. Indeed Cosenza and KShler (5) and others (2, 6, 7) using mouse antimouse idiotypic antisera have dearly demonstrated that anti-PC antibody from BALB/c possesses antigenic determinants shared by HOPC 8. Paradoxically however, antibodies from other strains, such as C57BL/6, A, and CE mice (2, 5-7), do not have this idiotypic specificity even though their antibody specificity cannot be distinguished from that of BALB/c. These studies indicate that variable-region determinants differ in the anti-PC antibodies of different strains of mice, but since the hapten inhibition of binding to idiotype was not studied, it is not dear that these idiotypic differences lie in the binding region. This consideration is crucial to the analysis of antibody combining-site diversity since selective pressures exerted on binding site and nonbinding site regions may be different.

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Section: Extent Of Shared Idiotypy On Hopc 8 and Mouse Anti-pc Antibocontrasting

confidence: 55%

Section: Extent Of Shared Idiotypy On Hopc 8 and Mouse Anti-pc Antibomentioning

confidence: 99%

Clonal Nature of the Immune Response to Phosphorylcholine

Claflin

Davie

1974

The Journal of Experimental Medicine

102

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“…It was, therefore, an exciting finding when in family studies with rabbits the inheritance of idiotypic specificities with the help of antiidiotypic reagents and the familial trait of isoelectric focusing spectra of specific antibodies was shown in comparison to a control rabbit population (5,17). These results were indicative for inheritance patterns of specific variable domains and did not conform to a random mutation concept within the variable regions of heavy and light antibody polypeptide chains.…”

mentioning

confidence: 67%

“…Antibodies of restricted heterogeneity, respectively homogeneity and monoclonal hybridoma-derived antibodies unlike myeloma proteins bear the expectation not only to comprehend the mechanisms of molecular interaction with the specific eliciting and cross-reactive antigen(s) but to understand in greater detail the enigma of antibody diversity. Heritable idiotype specificities and heritable isoelectric focusing characteristics of specific antibodies with known and programmed determinant (hapten) specificity (5,17,34,39) require the description of the structural correlates, i.e. the amino acid sequence as a final proof for validity (4).…”

Section: E Variable Region Amino Acid Sequences and Genetics Of Homomentioning

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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“…This number would be comfortably contained in a VH-pOO1 of 5000 genes. The stable inheritance of specific V-genes can be shown using the phenotypic markers, isoelectric focusing spectrum and idiotype (7,(20)(21)(22)(23). The overall stability of the V-gene pools remains to be established.…”

Section: Discussionmentioning

confidence: 99%

Germ Line Basis for Antibody Diversity: Immunoglobulin V _H - and C _H -gene Frequencies Measured by DNA·RNA Hybridization

Premkumar¹,

Shoyab²,

Williamson³

1974

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

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The reiteration frequency for mouse im- Immunoglobulin heavy (H) or light (L) chain structure can be explained by assuming that each chain is encoded by two genes, one variable (V)-and one constant (C)-gene (1). Heavy chains of all classes share the sme VH-gene pool and different CH-genes can be linked to the same VH-gene. One implication of this two gene-one polypeptide chain hypothesis is that there is no necessity for an equal number of V-and C-genes in the germ line. This satisfies the genetic evidence for a single C-gene for each constant region while permitting multiple V-genes as implied by amino-acid sequence data. That data points to a minimum essential number of V-genes which could account for the extent of antibody diversity only if there is a superimposed somatic generation of diversity (2-5). Alternatively a larger number of V-genes could be present in the germ-line and this could easily be a sufficient number to code for the total repetoire of antibodies without invoking diversification (1, 6, 7). A direct estimate of the reiteration frequency of a given gene can be made by hybridization of a suitable radioactive probe, either RNA or DNA, in the presence of a vast excess of DNA (8). The probe, either mRNA or a reverse transcript thereof, must be labeled at very high specific activity so that the vast excess of DNA can be achieved.We have used as a probe the mRNA for the a-chain of mouse myeloma protein 315. The mRNA was labeled in 315 cells grown in tissue culture and was isolated by virtue of its specific interaction with immunoglobulin (refs 9 and 10, Premkumar, Stevens, and Williamson, in preparation (11), and the total RNA was isolated from the cytoplasmic fraction by the phenol-chloroform method of Singer and Penman (12). After phenol extraction, the RNA was precipitated with 2 volumes of ethanol overnight at -20°.The RNA precipitates were collected by centrifugation, dissolved in water, and fractionated into poly(A) containing RNA and nonpoly(A) RNA by the method of Schutz, Beato, and Feigelson (13). The poly(A) containing RNA fraction was precipitated with 3 volumes of ethanol overnight at -20°.The precipitate was collected by centrifugation, dissolved in 0.5 ml of solution A [0.5 mM MgCl2-75 mM NaCl-20 mM phosphate buffer (pH 7.6)], 50,g of 315 protein, purified by affinity chromatography on DNP-Sepharose column (14), in Solution A was added and the mixture incubated on ice for 3 min. Anti-315 antibody, purified on DEAE-Sephadex, was added at equivalence and the mixture was incubated on ice for a further 5 min (9). The precipitates formed were collected by centrifugation (3000 X g for 10 min) and washed three times with ice cold solution A. The precipitates were dissolved in 0.5 ml of 0.5% sodium dodecyl sulfate (SDS) solution and then diluted to 5 ml with RNA extraction buffer (0.1 M sodium acetate-0.2 M NaCl-1 mM EDTA-0.2% SDS), pH brought to 5.0 with acetic acid, and shaken with an equal volume of phenol-chloroform (3:1) mixture at 450 for 3 min.The mixture was then chilled, cen...

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The Inheritance of Individual Antigenic Specificities of Rabbit Antibodies to Streptococcal Carbohydrates

Cited by 136 publications

References 33 publications

Clonal Nature of the Immune Response to Phosphorylcholine

Clonal Nature of the Immune Response to Phosphorylcholine

The Use of Streptococcal Antigens to Probe the Mechanisms of Immunity

Germ Line Basis for Antibody Diversity: Immunoglobulin V _H - and C _H -gene Frequencies Measured by DNA·RNA Hybridization

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The Inheritance of Individual Antigenic Specificities of Rabbit Antibodies to Streptococcal Carbohydrates

Cited by 136 publications

References 33 publications

Clonal Nature of the Immune Response to Phosphorylcholine

Clonal Nature of the Immune Response to Phosphorylcholine

The Use of Streptococcal Antigens to Probe the Mechanisms of Immunity

Germ Line Basis for Antibody Diversity: Immunoglobulin V H - and C H -gene Frequencies Measured by DNA·RNA Hybridization

Contact Info

Product

Resources

About

Germ Line Basis for Antibody Diversity: Immunoglobulin V _H - and C _H -gene Frequencies Measured by DNA·RNA Hybridization