The immune response against anti‐idiotope antibodies. I. Induction of idiotope‐bearing antibodies and analysis of the idiotope repertoire

Takemori, Toshitada; Tesch, Hans; Reth, Michael; Rajewsky, Klaus

doi:10.1002/eji.1830121210

Cited by 61 publications

(57 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The monoclonal antibodies used in the present study have been described previously ([9, 101 see also [14]). B1-8 (NPbinding, IgM, h,) and TEPC 183 (IgM, x) were purified from ascites fluid by boric acid precipitation followed by filtration through Sephacryl S300 (Pharmacia Fine Chemicals, Uppsala, Sweden).…”

Section: Antibodiesmentioning

confidence: 99%

“…Monoclonal rat anti-mouse chain antibody was obtained from culture supernatant of the hybrid cell line R33-24 and purified over TEPC183-coupled Sepharose 4B [22]. The preparation and purification of goat anti-x antiserum has been described previously [14].…”

Section: Antibodiesmentioning

confidence: 99%

“…It is therefore not surprising that B1-8 Id are regularly expressed in anti-NP responses of those animals [lo, 131. However, B1-8 Id are not confined to NP-binding antibody molecules [14,151. At least one of them, Id Ac38, is expressed on the products of several closely related VH genes, one of which is the VH gene expressed in antibody B1-8 111, 16, 171.…”

Section: Introductionmentioning

confidence: 98%

See 2 more Smart Citations

The expression of a set of antibody variable regions in lipopolysaccharide‐reactive B cells at various stages of ontogeny and its control by anti‐idiotypic antibody

1983

Self Cite

View full text Add to dashboard Cite

An analysis is presented in which we measure the expression of a subset of antibody variable (V) regions in lipopolysaccharide (LPS)-reactive precursor B cells at various stages of ontogeny. The V regions were characterized by hapten (4-hydroxy-3-nitrophenyl)acetyl (NP)-binding specifity and/or expression of idiotypic determinants whose genetic basis had been explored in previous studies. Only V regions containing the V lambda 1 domain were considered: this allowed an unequivocal determination of idiotopes and reduced heterogeneity in the system essentially to the multiplicity of VH and D genes. It was found that approximately every fourth lambda 1-bearing LPS-reactive splenic B cell produces an NP-binding antibody. Approximately 1 in 40 lambda 1-bearing cells expressed an idiotope (Ac38) which is encoded by V lambda 1 and a set of related VH genes in combination with D and J elements. Of these cells, only a minority produce an NP-binding antibody and a few percent of the latter express a second idiotope (Ac146) which is known to be restricted to a subset of Ac38-positive, NP-binding humoral antibodies. All these frequencies are in good accord with previous analyses of anti-idiotope-induced antibodies in the serum. They can be easily accommodated into a simple model of random selection of VH genes in LPS-reactive B lymphocytes. The frequencies of the V regions under study were essentially the same in LPS-reactive B cells from spleens of adult and newborn animals and in LPS-reactive B cells generated from bone marrow pre-B cells in vitro. In the case of the latter cells the frequencies were independent of the absence or presence of T cells in the culture system. While we could thus detect, in naive mice, neither positive nor negative selection of the cells from the time of their generation in the bone marrow until their arrival in the periphery, negative selection is in principle possible: the presence of microgram amounts of anti-idiotope antibodies during maturation from pre-B to B cells specifically blocks the appearance of idiotope-bearing LPS-reactive cells in vitro. The potential physiological role of the latter effect in the sense of self-stabilization of the expressed antibody repertoire in ongoing immune responses and the possibility that frequency determinations in LPS-reactive B cells may be not representative for the repertoire expressed in the population of mature B cells is discussed.

show abstract

Section: Antibodiesmentioning

confidence: 99%

Section: Antibodiesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

See 1 more Smart Citation

The expression of a set of antibody variable regions in lipopolysaccharide‐reactive B cells at various stages of ontogeny and its control by anti‐idiotypic antibody

1983

Self Cite

View full text Add to dashboard Cite

show abstract

“…and Rajewsky,K., in preparation). This antibody is produced by a hybridoma derived from cells of C57BL/6 mice immunized with anti-idiotope antibody Ac 38 (Roth et al, 1979;Takemori et al, 1982). It contains the Npb idiotope but does not bind Np ligands.…”

Section: Discussionmentioning

confidence: 99%

“…The use of different genes in the anti-NP response by BALB/c mice is therefore not due to the absence of VH genes which are similar to those used by C57BL/6 mice. In fact, BALB/c mice are capable of producing immunoglobulins, which carry the Npb idiotype of C57BL/6 anti-NP antibodies (Takemori et al, 1982). These BALB/c Npb immunoglobulins, which can be induced by immunization with antibodies that are specifically directed against the Npb idiotype, however, do not bind NP.…”

Section: Introductionmentioning

confidence: 99%

Allelic immunoglobulin VH genes in two mouse strains: possible germline gene recombination.

Cohen¹

1983

The EMBO Journal

View full text Add to dashboard Cite

The nucleotide sequence of two germline immunoglobulin heavy chain variable region (VH) genes of mouse BALB/c origin was determined. These two genes are highly homologous to each other. They both have the unusual codon CCT for proline at position 7, which so far has been found only in a specific set of VH genes, called the Npb family. We show that the two VH genes belong to this set. One of our BALB/c genes, VH124, is more homologous to a C57BL/6 Npb VH gene than to any BALB/c VH gene, and we propose that these two genes are alleles. A comparison of the substitutions between these two genes with published sequences of all other BALB/c and C57BL/6 Npb VH genes reveals evidence for past homologous recombination events between related germline VH genes. Homologous recombination may play an important role in the diversification of germline immunoglobulin VH genes.

show abstract

The immune response against anti‐idiotope antibodies II. The induction of antibodies bearing the target idiotope (Ab3β) depends on the frequency of the corresponding B cells

Tesch

Takemori²,

Rajewsky³

1983

Eur J Immunol

Self Cite

View full text Add to dashboard Cite

In the present study we use two monoclonal anti-idiotope antibodies (Ac38 and Ac146; Ab1) against the germ line-encoded, lambda 1 chain-bearing and (4-hydroxy-3-nitrophenyl)acetyl (NP)-binding antibody B1-8 (Ab1) for the induction of complementary antibodies (Ab3) and ask the question to what extent antibodies bearing B1-8-like idiotopes (Ab3 beta) are represented in the Ab3 population. In this experimental system, Ab3 beta is distinguished from the remaining Ab3 population (Ab3 alpha) by three properties which Ab3 beta may share with B1-8: (a) the binding of NP, (b) the binding to Ac146 (if induced by Ac38) or the binding to Ac38 (if induced by 146) and (c) that they carry lambda 1 chains. Antibodies with all three properties are induced in low amounts by both anti-idiotopes. Also, Ac146 induces only Ab3 alpha (bearing kappa chains and not binding NP and Ac38). In contrast, Ac38 triggers almost exclusively a lambda 1 chain-bearing response, i.e. Ab3 beta. The response has an unusually large size, reaches its maximum after a week and is long-lasting. An analysis at the level of lipopolysaccharide-reactive precursor B cells demonstrates that, in this case, cells expressing Ab3 beta occur at exceedingly high frequency (approximately equal to 10(-3] and are at least 10 times more frequent than cells expressing Ab3 alpha. The high frequency of Ab3 beta-expressing cells correlates with the contribution of several VH, D and J genes to the expression of this particular idiotope. In the case of the Ac146 anti-idiotope antibody, the response is dominated by Ab3 alpha. Ab3 beta represents less than 10% of the total response, reaches maximal levels 2 weeks after immunization and declines rapidly. This correlates with a low frequency of precursor B cells expressing Ab3 beta (approximately equal to 10(-5] and a restriction of the corresponding idiotope to rare VH-D combinations, caused presumably by a stringent contribution of the H chain to this idiotope which covers the NP-binding site. Our data suggest that anti-idiotypic antibodies (Ab2) against Ab1 will preferentially induce antibodies idiotypically related to Ab1 if the corresponding idiotopes are expressed in high frequency in the B cell compartment. This is expected in cases where Ab2 recognizes an idiotope that can be formed by many germ line-encoded VH-D-VL-combinations.

show abstract

The immune response against anti‐idiotope antibodies. I. Induction of idiotope‐bearing antibodies and analysis of the idiotope repertoire

Cited by 61 publications

References 43 publications

The expression of a set of antibody variable regions in lipopolysaccharide‐reactive B cells at various stages of ontogeny and its control by anti‐idiotypic antibody

The expression of a set of antibody variable regions in lipopolysaccharide‐reactive B cells at various stages of ontogeny and its control by anti‐idiotypic antibody

Allelic immunoglobulin VH genes in two mouse strains: possible germline gene recombination.

The immune response against anti‐idiotope antibodies II. The induction of antibodies bearing the target idiotope (Ab3β) depends on the frequency of the corresponding B cells

Contact Info

Product

Resources

About