Specificity and idiotypic analysis of monoclonal antibodies directed against the MOPC460 idiotype

Sanchez, Pierre; Guern, Christian Le; Phalente, Laurent; Barbier, Eliane; Buttin, Gérard; Cazenave, Pierre‐André

doi:10.1016/0161-5890(82)90354-6

Cited by 9 publications

(2 citation statements)

References 18 publications

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“…For several years the existence of idiotype-positive immunoglobulins without detectable antibody function has excited considerable speculation (reviewed in 6). The antibody response (Ab3) of animals immunized with anti-idiotypic antibodies has particularly been studied (4,(6)(7)(8)(9)(10)(11)(12)(13)(14). These responses are generally characterized by antibodies idiotypically similar to Abl but they may not recognize antigen.…”

Section: Resultsmentioning

confidence: 99%

The relationship between variable region determinants and antigen specificity on mitogen reactive B cell subsets.

Primi¹,

Mami²,

Guern³

et al. 1982

The Journal of Experimental Medicine

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Recently we determined the absolute frequencies of lipopolysaccharide (LPS) and Nocardia-delipidated cell mitogen (NDCM) -sensitive B lymphocytes from BALB/c mice secreting immunoglobulin (Ig) molecules bearing any one of three different idiotopes originally found on a monoclonal anti-fl-galactosidase antibody (1). These three idiotopes, 66, 137 and 395, are defined by syngeneic monoclonal antibodies against the monoclonal Ig 174 produced by a BALB/c mouse (C. Le Guern, E. Barbier, and D. Juy. Idiotypic heterogeneity of monoclonal anti-fl-galactosidase antibodies. Manuscript in preparation). Extensive studies by conventional immunization clearly demonstrated that these three determinants are not normally expressed at detectable level when BALB/c mice are immnized with fl-galactosidase and, therefore, can be classified as nonrecurrent idiotopes (Le Guern et al., see above). Our results, however, indicate that these specificities are not only part of the idiotypic repertoire of LPS-and NDCM-sensitive BALB/c B cells, but that they can be induced to expression with a frequency similar to that of a recurrent idiotype, i.e., M-460 (1, 2). Because the frequency of a given specificity (either antibody or idiotypic specificity) determined by mitogenic stimulation does not require the presence of antigen, this analysis was not dependent on a particular protocol of immunization, but rather reflected the absolute frequencies of competent B cells in a steady state. Thus the discrepancy found between antigenic and polyclonal activation with regard to idiotope(s) expression may very well reflect independent expression of these V region markers and antigen-binding sites. The existence of defined idiotopes on immunoglobulins without known antigen specificity has been fully documented for some considerable time (3-6) but, up until now, it has been difficult to establish the possible existence of well-defined rules that govern the relationship between idiotopes and antigen-binding sites. Such studies have been hampered by the difficulty of selecting B cell clones or hybridomas that are positive or negative for any possible combination of a number of well-defined sets of V regions. Here, however, we were able to address this problem, because we knew the absolute frequencies of each of our three idiotopes and therefore could select and study individual clones of mitogenreactive B cells positive for any possible combination of these determinants and correlate them to anti-/~-galactosidase activity. The results presented here indicate

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Section: Resultsmentioning

confidence: 99%

The relationship between variable region determinants and antigen specificity on mitogen reactive B cell subsets.

Primi¹,

Mami²,

Guern³

et al. 1982

The Journal of Experimental Medicine

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“…Idiotope detection was carried out by inhibition test as previously described [11]. For the analysis of the anti-DNP immune response, the antisera were diluted at 1 : 5.…”

Section: Radioimmunoassay (Ria)mentioning

confidence: 99%

Allotypic restriction of the expression of MOPC460 idiotope after immunization with either anti‐2,4‐dinitrophenyl (DNP) or anti‐idiotypic antibodies

1983

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Restrictive idiotope expression 999The MOPC460 idiotype is expressed in mice with the IghC" allotypic haplotype after anti-2,4-dinitrophenyl (DNP) immunization. We have previously shown that two monoclonal syngeneic anti-idiotypic antibodies (IDM 92-13 and IDM 41-27) define two distinct idiotopes (the 460.92 and the 460.41) on the M460 idiotype. The current study demonstrates that only one idiotope (460.92) is recurrently expressed after antigen immunization in IghC" positive mice and also that, immunization against the monoclonal anti-idiotypic molecules induces the synthesis of 460.92 idiotope positive anti-DNP antibodies. However, the detection of such molecules is only possible when animals with the IghC" allotypic haplotype are immunized with the IDM 92-13 molecules. Immunization of mice with either of the two monoclonal anti-idiotypic antibodies never results in the synthesis 460.41 positive molecules. Therefore, whatever protocol of immunization used, the expression of 460.92 was allotypic restricted.

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The regulatory locus rλ1 affects the level of λl light chain synthesis in lipopolysaccharide‐activated lymphocytes but not the frequency of λl ‐positive B cell precursors

Sanchez¹,

Primi²,

Levi-Strauss³

et al. 1985

Eur J Immunol

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Several strains of mice, most notably the SJL strain, have a greatly reduced level of circulating lambda 1 immunoglobulins (r lambda 1 lo phenotype) compared with other mice. The locus responsible for this phenotype has been shown to be closely linked to the structural C lambda 1 gene. Functionally this locus has been said to reduce the number of lymphocytes expressing surface lambda 1 molecules. In order to gain a better understanding of this phenomenon we compared the functional properties of activated B cells secreting lambda 1 immunoglobulins in the splenocytes of both BALB/c and SJL mice. Our results indicate that regulatory T cells, as well as regulatory ontogenetic processes, are not responsible for the r lambda 1 lo phenotype. In addition, limiting dilution analyses revealed that the number of lipopolysaccharide-sensitive precursors of lambda 1-secreting B cells was similar in the splenocytes of the two strains of mice tested. The quantity of lambda 1 molecules produced by a B cell clone, however, was found to be lower in SJL than in BALB/c mice. As the level of lambda 1 mRNA is greatly reduced in lipopolysaccharide blasts of SJL mice, as compared to the mRNA detected in BALB/c blasts, we conclude that the impairment responsible for the r lambda 1lo phenotype is probably transcriptional. We tentatively propose that sequences 5' to the C lambda 1 region are defective in their capacity to enhance the lambda 1 transcripts in SJL mice.

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Specificity and idiotypic analysis of monoclonal antibodies directed against the MOPC460 idiotype

Cited by 9 publications

References 18 publications

The relationship between variable region determinants and antigen specificity on mitogen reactive B cell subsets.

The relationship between variable region determinants and antigen specificity on mitogen reactive B cell subsets.

Allotypic restriction of the expression of MOPC460 idiotope after immunization with either anti‐2,4‐dinitrophenyl (DNP) or anti‐idiotypic antibodies

The regulatory locus rλ1 affects the level of λl light chain synthesis in lipopolysaccharide‐activated lymphocytes but not the frequency of λl ‐positive B cell precursors

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