The Immune Response to the Alpha 1–6 Epitope of Dextran is Determined by a Gene Linked to the IgCH Locus

Fernández, Carmen; Lieberman, Rose; Möller, Göran

doi:10.1111/j.1365-3083.1979.tb01337.x

Cited by 40 publications

(25 citation statements)

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“…The responsiveness of various mouse strains to the TI antigen Dex B512 has been claimed to be controlled by genes linked to the IgCH locus [7], nonresponder mice actually lacking all VH genes capable of encoding Dex-specific antibodies [2]. Recently, however, we found that the responses to Dex, both among high-and low-responder mice, are so variable in magnitude that such traits cannot unequivocally be concluded, let alone linked to a particular genetic locus [ll].…”

Section: Discussionmentioning

confidence: 99%

“…Fernandez and colleagues have reported that the magnitude of the splenic plaque-forming cell (PFC) responses to Dex is controlled by heavy chain allotype locus (1gCH)-linked genes [7], which is a feature shared by the immune response to other antigens as well [8]. This was interpreted to indicate that, depending on the IgVH gene pools, different mouse strains would produce Dex-specific B lymphocytes in different frequencies l7].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The immune response to bacterial dextrans III. Ontogenic development and strain distribution of specific clonal precursors

Lundkvist¹,

Holmberg²,

Ivars³

et al. 1986

Eur J Immunol

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The frequencies of B512 dextran (Dex)-specific B cell precursors were determined by limiting dilution analysis in a number of mouse strains originally described as "high responder", "low responder" and "nonresponder" to this antigen. No significant difference in the frequencies of Dex-specific precursors was found in C57BL/6, B10.BR, C3H/Tif, BALB/c and A/Sn adult mice. Together with the large intra-strain variability in the magnitude of anti-Dex PFC responses in vivo, these results established that differential reactivity in vivo cannot be ascribed to genetically controlled absence or wide variation in the frequency of Dex-specific immunocompetent precursors. A similar analysis of the Dex-specific precursor frequency was carried out in C57BL/6 mice between 1 week and 3 months of age. While no Dex-specific antibody response was detected in vivo before the age of 3 weeks, clonal precursor analysis revealed that the appearance of these specificities parallels the development of competent (IgM-producing) B lymphocyte clonal precursors, such that no significant difference in absolute frequencies of Dex-specific precursors could be observed among these age groups. This is interpreted to suggest that the late development of the Dex-specific antibody responses is regulatory rather than due to late rearrangement and activation of the appropriate V genes and a sequential expression of antibody specificities in ontogenic development.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The immune response to bacterial dextrans III. Ontogenic development and strain distribution of specific clonal precursors

Lundkvist¹,

Holmberg²,

Ivars³

et al. 1986

Eur J Immunol

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“…Dextran B512 is a homopolymer of glucose consisting of 95% a(1-6)-linked glucose, with 5% a(1-*3)-linked glucose at branch points (1,2), and dextran-specific antibodies have been described in humans (3,4), rabbits (5), and mice (6)(7)(8)(9)(10). The simplicity of the antigenic determinant and the availability of oligosaccharides provided a molecular ruler for measuring the sizes of anti-dextran combining sites (3,4).…”

mentioning

confidence: 99%

Nucleotide sequence of the cDNAs encoding the variable region heavy and light chains of a myeloma protein specific for the terminal nonreducing end of alpha(1----6)dextran.

Borden¹,

Kabat²

1987

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

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The complete nucleotide sequences of the cDNAs encoding the heavy-and light-chain variable regions (VH and VL) of myeloma protein W3129, an anti-a(1--+6)-dextran with a unique combining site, have been determined. The VH region is encoded by a germ-line gene highly homologous to VH441, which also appears to be used in some anti-galactans and anti-levans. W3129 VH uses a diversity region that is not found in any of the galactan-or levan-specific antibodies and whose germ-line counterpart is unknown. The W3129 light chain differs from complete light-chain sequences thus far reported but is identical in the rwst 23 amino acids with NZB IgA myeloma PC118.Dextran B512 is a homopolymer of glucose consisting of 95% a(1-6)-linked glucose, with 5% a(1-*3)-linked glucose at branch points (1, 2), and dextran-specific antibodies have been described in humans (3, 4), rabbits (5), and mice (6-10). The simplicity of the antigenic determinant and the availability of oligosaccharides provided a molecular ruler for measuring the sizes of anti-dextran combining sites (3, 4). Isolation of mouse myelomas specific for a(1--6)dextran allowed detailed immunochemical mapping of the combining site sizes and shapes of homogeneous populations of antibodies. These monoclonal antibodies recognize either the internal linear portion of the molecule or the terminal nonreducing ends; the former were loosely described as having groove-shaped sites, and the latter as having cavityshaped sites. Two such myeloma proteins, QUPC52 and W3129, served as prototypes for groove-type and cavity-type combining sites, respectively. QUPC52 has a combining site size complementary to 6 a(1-*6)-linked glucose units, whereas the site size ofW3129 is 5 glucose units, with glucoses from the nonreducing end (11, 12), and possibly internal residues (13), contributing =95% of the binding energy. This distinction has been made by inhibition of precipitation of a(1-6)dextran with dextran-specific antibodies, using oligosaccharides ranging in size from 2 to 7 a(1-*6)-linked glucose units (11), by competition in equilibrium dialysis (12), and by fluorescence quenching experiments (12,14). Moreover, a synthetic linear dextran of 200 glucose units (15) behaves as a monovalent nonprecipitating ligand for W3129 since it has but one terminal nonreducing end (12), whereas it precipitates with QUPC52, since any 6 of the 200 a(1-36)-linked glucoses could constitute a determinant, and thus it would be multivalent toward groove-type sites. Precipitation with synthetic linear dextran thus provides a rapid method of distinguishing between these two kinds of sites.Numerous mouse hybridomas secreting antibodies specific for a(1-36)-linked dextran have been generated in this laboratory; all are reactive with the internal linear portion of the dextran molecule (6-8). Thus, although cavity-type antibodies have been described in the serum of rabbits (16), only two monoclonal antibodies, W3129 and W3434, have been reported (11) that recognize the terminal nonreducing end ofthe dextra...

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“…Native dextran B 512 is a thymus-independent antigen that gives rise to a mono-or oligoclonal immune response against the a 1-6 epitope (1, 2). The ability to give an IgM immune response to dextran B 512 is determined by one gene linked to two heavy-chain allotype markers (Ig-1 b and j) (3) characteristic of the strains C57BL and CBA, respectively (4). However, these two strains differ markedly with regard to several characteristics of the response to the a 1-6 epitope of dextran.…”

mentioning

confidence: 99%

“…However, these two strains differ markedly with regard to several characteristics of the response to the a 1-6 epitope of dextran. Thus, CBA mice give only an IgM response, whereas C57BL produce both IgM and IgG (5). After induction of a primary immune response with an optimal dose of dextran, both strains fail to respond to a second challenge with the same antigen.…”

mentioning

confidence: 99%

Antigen-induced strain-specific autoantiidiotypic antibodies modulate the immune response to dextran B 512.

Fernández¹,

Möller²

1979

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

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Sera from CBA and C57BL mice immunized against dextran B 512 eight or more days earlier contain mainly IgG antibodies that specifically suppress the development of plaque-forming cells against dextran in vitro. Suppression was not caused by antibodies against the a 1-6 epitope of dextran to any mapor extent. Sera from CBA mice (IgCH allotype j) suppressed plaque-forming cells from CBA mice, whereas sera from C57BL mice (allotype b) inhibited plaques from C57BL

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The Immune Response to the Alpha 1–6 Epitope of Dextran is Determined by a Gene Linked to the IgCH Locus

Cited by 40 publications

References 13 publications

The immune response to bacterial dextrans III. Ontogenic development and strain distribution of specific clonal precursors

The immune response to bacterial dextrans III. Ontogenic development and strain distribution of specific clonal precursors

Nucleotide sequence of the cDNAs encoding the variable region heavy and light chains of a myeloma protein specific for the terminal nonreducing end of alpha(1----6)dextran.

Antigen-induced strain-specific autoantiidiotypic antibodies modulate the immune response to dextran B 512.

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