The Role of Receptor IgM and IgD in Determining Triggering and Induction of Tolerance in Murine B Cells<sup>1</sup>

Kettman, John R.; Cambier, John C.; Uhr, Jonathan W.; Ligler, Frances S.; Vitetta, Ellen S.

doi:10.1111/j.1600-065x.1979.tb00418.x

Cited by 49 publications

(19 citation statements)

References 55 publications

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“…Experiments designed to test such hypotheses have been reviewed (27)(28)(29). Sidman and Unanue (30) and Sieckmann et al (31) have shown by cell sorting experiments that the subset of B cells which responds to anti-pt antibodies by DNA synthesis has relatively large amounts of sIgD.…”

Section: Discussionmentioning

confidence: 99%

Activation of murine B lymphocytes by anti-immunoglobulin is an inductive signal leading to immunoglobulin secretion.

Parker¹,

Wadsworth²,

Schneider³

1980

The Journal of Experimental Medicine

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Cultures of isolated mouse splenic B lymphocytes activated by the divalent F(ab')2 fragment of purified rabbit anti-mouse Fab or class-specific anti-mouse IgM antibodies can be driven on to high rate Ig secretion by the addition of the supernatant fluid of a 24-h culture of concanavalin A-activated spleen cells (SN). The polyclonal antibody response to anti-Ig pus SN is comparable in magnitude with the lipopolysaccharide response as measured in a reverse plaque assay. The addition of SN can be delayed for 24 h after addition of anti-Ig without changing the kinetics of the response. Addition at 48 h delays the response by 24 h. The response to F(ab')2 anti-Fab plus SN is sensitive to Fc-dependent inhibition because intact anti-Fab antibodies inhibit strongly at relatively low concentrations. The monovalent Fab' fragment fails to induce Ig secretion, indicating that cross-linkage of surface immunoglobulin is required. Although the production of active SN is T cell dependent, the response to anti-Ig plus SN is T independent. These findings are interpreted as a polyclonal model of a thymus-dependent antibody response. X

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Section: Discussionmentioning

confidence: 99%

Activation of murine B lymphocytes by anti-immunoglobulin is an inductive signal leading to immunoglobulin secretion.

Parker¹,

Wadsworth²,

Schneider³

1980

The Journal of Experimental Medicine

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“…The reasons include: (i) the low concentration of serum IgD except in rare patients with multiple myeloma, (ii) the apparent lack of a characteristic antibody activity or effector function, (iii) the extreme sensitivity of IgD to "spontaneous" proteolytic degradation (1,9), and (iv) the unusual structure of the hinge region, which presented difficult technical problems for its determination (5,6). However, mounting evidence that this minor class ofcirculating immunoglobulins has a major function as an antigen receptor on the membrane of B lymphocytes (10,11) led us to undertake determination of the complete primary structure of human IgD. We have reported the complete amino acid sequence of the Fc region (2) and of the C81 and hinge regions (3), which together constitute the entire constant (C) region ofthe 8 chain of the myeloma protein WAH.…”

mentioning

confidence: 99%

“…Interest in the structure of IgD was stimulated by evidence that it functions as a major receptor on the surface of B lymphocytes, where it is coexpressed with IgM after antigen capture triggers cell differentiation (10,11). Like IgM, IgD exists in two forms: sIgD, which is secreted into the serum, and mIgD, which is bound to the B-cell membrane.…”

mentioning

confidence: 99%

“…Cloning studies (12)(13)(14)(15)(16) have shown that the A& and 8 structural genes may both be expressed in a single primary transcript that can be processed to yield either IgM or IgD having the same VH region. Although the recent findings on the cellular role and biosynthesis of tL and 8 chains are similar for mice and humans (9)(10)(11)(12)(13)(14)(15)(16), and although human and mouse IgM are similar in structure (17,18), the mouse 8 chain is unusual in that it lacks the C82 domain present in the human 8 chain (1-7). The hinge structures of the 8 chains ofthe two species also differ, and there is unexpectedly low homology in the C81 domains (3).…”

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confidence: 99%

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Complete amino acid sequence of the delta heavy chain of human immunoglobulin D.

Takahashi¹,

Tétaert²,

Debuire³

et al. 1982

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

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We have determined the amino acid sequence of the variable (V) region of the 8 heavy (H) chain of human IgD isolated from the plasma of myeloma patient WAH. This V region is unusual in its amino end group (arginine) and in its length (129 residues). The length is due to 10 insertions in the third complementarity-determining region (CDR3). A computer search showed that no reported CDR3-joining region (-JH) sequences are identical and that they appear to be unrelated to the constant (C) region sequences of immunoglobulins. The V region sequence together with our previous results for the C region give the complete sequence of the human 8 chain WAH, which has 512 amino acid residues and a Mr 65,000. The human 8 chain has four domains (V, C81, C82, and C83) and a long hinge region; by comparison, the mouse 8 chain lacks a continuous segment of 135 residues, including half the hinge region and the entire C82 domain. The human and mouse 8 chains also differ in the number, kind, and location ofGlcN and GalN glycans and probably in conformation and quaternary structure. These and other considerations suggest that there may be multiple forms of both secreted and membranebound IgD that differ in size, structure, and function.Although sequence data have been published for more than 50,000 amino acid residues of immunoglobulins of various classes and species, until recently (1-8) little was known about the amino acid sequence of human IgD. The reasons include: (i) the low concentration of serum IgD except in rare patients with multiple myeloma, (ii) the apparent lack of a characteristic antibody activity or effector function, (iii) the extreme sensitivity of IgD to "spontaneous" proteolytic degradation (1, 9), and (iv) the unusual structure of the hinge region, which presented difficult technical problems for its determination (5, 6). However, mounting evidence that this minor class ofcirculating immunoglobulins has a major function as an antigen receptor on the membrane of B lymphocytes (10, 11) led us to undertake determination of the complete primary structure of human IgD. We have reported the complete amino acid sequence of the Fc region (2) and of the C81 and hinge regions (3), which together constitute the entire constant (C) region ofthe 8 chain of the myeloma protein WAH. Here, we report the structure ofthe variable (V) region ofthe heavy (H) chain (the VH region), which completes the amino acid sequence of the 8 H chain; in work to be reported separately, we have determined the entire sequence ofthe A light (L) chain, which completes the structure of a human IgD molecule.Interest in the structure of IgD was stimulated by evidence that it functions as a major receptor on the surface of B lymphocytes, where it is coexpressed with IgM after antigen capture triggers cell differentiation (10, 11). Like IgM, IgD exists in two forms: sIgD, which is secreted into the serum, and mIgD, which is bound to the B-cell membrane. Cloning studies (12)(13)(14)(15)(16) have shown that the A& and 8 structural genes may both b...

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“…Yet, interest in its structure has intensified because of evidence that IgD exists in two forms (3,4): the IgD secreted into the serum and the IgD bound to the surface membrane of B lymphocytes, where it functions as a receptor (5). Whereas the 8 heavy chain of human IgD has a four-domain structure consisting of a variable (VH) region and three constant (C) region domains (C51, C82, and C83) (1,2,6), DNA sequence analysis ofthe gene coding for a mouse 8 chain (7) indicates the presence of only two C region domains, designated C,61 and C&3 with an apparent deletion of C82.…”

mentioning

confidence: 99%

Amino acid sequence of the first constant region domain and the hinge region of the delta heavy chain of human IgD.

Putnam¹,

Takahashi²,

Tétaert³

et al. 1981

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

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BiochemistryAmino acid sequence of the first constant region domain and the hinge region of the 6 heavy chain of human IgD ( ABSTRACT We have determined the amino acid sequence of the first constant (C) region domain (C61) and the hinge region of the 6 heavy chain of human IgD WAH and also the sequence of the adjacent COOH-terminal portion of the variable (V) region, including the JH region. Together with the sequence ofthe Fc fragment already reported, this establishes the complete amino acid sequence of the C region of the human 8 chain and confirms the presence of three C region domains in human IgD. Although the CH1 domains of the five classes of human heavy chains have the expected degree of homology (='30%), the homology of the C,61 domains of the human and mouse chains is less than that exhibited by the CHI domains of other pairs of human and mouse heavy chains. The hinge region of the human 6 chain has an unusual structure; the NH2-terminal half has four (or five) GalN oligosaccharides attached, whereas the COOH-terminal half lacks carbohydrate, is dissimilar in sequence, and has a high charge. A computer search verified that the GalN-rich segment has a high degree of identity in sequence with the middle portion of the human C02 domain and that the high-charge segment is related to the same sequence. We propose that the two segments of the human 5 hinge have a common evolutionary origin and arose by duplication and independent mutation of a hinge exon derived from the ancestral gene for the C ,A2 domain.

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The Role of Receptor IgM and IgD in Determining Triggering and Induction of Tolerance in Murine B Cells¹

Cited by 49 publications

References 55 publications

Activation of murine B lymphocytes by anti-immunoglobulin is an inductive signal leading to immunoglobulin secretion.

Activation of murine B lymphocytes by anti-immunoglobulin is an inductive signal leading to immunoglobulin secretion.

Complete amino acid sequence of the delta heavy chain of human immunoglobulin D.

Amino acid sequence of the first constant region domain and the hinge region of the delta heavy chain of human IgD.

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The Role of Receptor IgM and IgD in Determining Triggering and Induction of Tolerance in Murine B Cells1

Cited by 49 publications

References 55 publications

Activation of murine B lymphocytes by anti-immunoglobulin is an inductive signal leading to immunoglobulin secretion.

Activation of murine B lymphocytes by anti-immunoglobulin is an inductive signal leading to immunoglobulin secretion.

Complete amino acid sequence of the delta heavy chain of human immunoglobulin D.

Amino acid sequence of the first constant region domain and the hinge region of the delta heavy chain of human IgD.

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The Role of Receptor IgM and IgD in Determining Triggering and Induction of Tolerance in Murine B Cells¹