Presence of serum IgD and IgD‐containing plasma cells in the mouse

Bargellesi, A.; Corte, Giorgio; Cosulich, Elisabetta; Ferrarini, Manlio

doi:10.1002/eji.1830090614

Cited by 28 publications

(8 citation statements)

References 15 publications

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“…Previous studies analyzing 8 chains from mixed populations ofcells or immunoglobulins have identified heterogeneity in the NaDodSO4 gel electrophoresis profiles of 8m and 8s (9,10,(13)(14)(15)(16)(17)(18)(19). This heterogeneity may be related to the observation, in the present investigation, of differential N-glycosylation of the SeD 8 chains.…”

Section: Methodssupporting

confidence: 51%

“…Studies using one-dimensional NaDodSO4 gel electrophoresis systems have demonstrated that am exists as two molecular entities (8im and 8m2), distinguished from one another by a difference in molecular weight (ranging from 2000 to 7000) (13)(14)(15)(16). Likewise, 8, has been resolved into two species (5s1 and 8s2) that differ in molecular weight (17)(18)(19). The relationship between these various forms ofthe 8 chain is obscure at present.…”

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confidence: 99%

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Biogenesis of membrane-bound and secreted immunoglobulins: two primary translation products of the human delta chain, differentially N-glycosylated to four discrete forms in vivo and in vitro.

McCune¹,

Fu²,

Kunkel³

et al. 1981

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

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Structural differences between the heavy chain of membrane IgD (Bin) and the heavy chain of secreted IgD (8s) were investigated by using a human lymphoblastoid cell line that expresses idiotypically identical IgM and IgD. In a wheat germ cell-free system, mRNA from this cell line was shown to encode two distinct 8 Further analysis of these functional systems must eventually be accompanied by a detailed structural examination ofthe IgD heavy chain (8). Until recently, the low incidence of IgD myeloma and the extreme lability of IgD to proteolysis hampered the determination of the Fc amino acid sequence of the heavy chain of secretory IgD (8,) (7). The study of the heavy chain of membrane IgD (Sm) has been even more difficult. It is extremely susceptible to proteolysis and is present in low amounts, with a slow turnover rate on B cell membranes. Early structural studies on membrane IgD demonstrated that reduced 8 chains migrate as a broad band on NaDodSO4/polyacrylamide gel electrophoresis (8, 9). Subsequent analyses by two-dimensional gel electrophoresis indicated that the biosynthetic forms of 8 exist as a heterogeneous group, reflective of modifications of N-linked oligosaccharides (10). As shown by charge-shift electrophoresis, these forms probably have a hydrophobic COOH terminus (11, 12). Studies using one-dimensional NaDodSO4 gel electrophoresis systems have demonstrated that am exists as two molecular entities (8im and 8m2), distinguished from one another by a difference in molecular weight (ranging from 2000 to 7000) (13-16). Likewise, 8, has been resolved into two species (5s1 and 8s2) that differ in molecular weight (17)(18)(19). The relationship between these various forms ofthe 8 chain is obscure at present. As a result, the structural relationships between 5im and 8, as well as those between am and ILm have yet to be resolved.In this study, IgD biosynthesis was analyzed in a human B lymphoblastoid cell line (SeD) that coexpresses IgM. All Ig molecules synthesized by this cell line express the same idiotype. The 8 chains of this line were found, by cell-free translation ofextracted mRNA, to exist as two distinct primary translation products, most likely corresponding to 8m and 8s. When followed by pulse-chase experiments in vivo, these chains were found to be processed to four forms, differing in relative mobility as a result of differential N-glycosylation. 8m appears to be a higher molecular weight than 8, and does not have a large cytoplasmically exposed domain. MATERIALS AND METHODSPreparation of RNA and Cell-Free Protein Synthesis. Total cellular RNA was extracted with NaDodSOjphenol/chloroform/isoamyl alcohol and proteinase K as described (20) and translated in a staphylococcal nuclease-treated wheat germ system (21).[35S]Methionine (New England Nuclear; 700 Ci/ mmol; 1 Ci = 3.7 x 10'°becquerels) was used at a final concentration of 1 mCi/ml, and salts were adjusted to final concentrations of 150 mM KOAc and 3.8 mM Mg(OAc)2. In indicated experiments, dog pancreatic microsomal membran...

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Section: Methodssupporting

confidence: 51%

mentioning

confidence: 99%

Biogenesis of membrane-bound and secreted immunoglobulins: two primary translation products of the human delta chain, differentially N-glycosylated to four discrete forms in vivo and in vitro.

McCune¹,

Fu²,

Kunkel³

et al. 1981

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

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“…Our analysis of TEPC 1017 may provide an answer for the mode of IgD secretion by tumors but it raises a more fundamental question concerning the mechanism utilized in the normal immune response. Even though IgD-secreting plasma-cell subsets have been identified in the spleen (50), levels of as chain mRNA (5,34) or protein (34) in spleen are barely detectable. We previously hypothesized (33,49), based on the presence of a as precursor mRNA in plasma cell-depleted splenic B cells (49), that the low levels of as message are transcribed from the (VDJ-Cg-Cs) unrearranged DNA template.…”

Section: Methodsmentioning

confidence: 99%

Illegitimate recombination generates a class switch from C mu to C delta in an IgD-secreting plasmacytoma.

Gilliam

Shen

Richards

et al. 1984

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

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“…It was previously determined that no DNA sequences resembling switch sites exist upstream of the mouse C8 gene (13,44). However, humans demonstrate a higher serum IgD content (2) and a higher occurrence of IgD myelomas (11) than do mice, suggesting that a switchlike mechanism may occur at the C. gene in humans. Indeed, after obtaining the sequence of the entire 19,800-base-pair (bp) region that * Corresponding author.…”

mentioning

confidence: 99%

Immunoglobulin D switching can occur through homologous recombination in human B cells.

White¹,

Word²,

Humphries³

et al. 1990

Mol. Cell. Biol.

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Prototypical class switching in mouse and human immunoglobulin heavy chains occurs through recombination of tandem blocks of short repeats located 5' to each heavy chain constant region (CH) except C8. Deletion of C, in immunoglobulin D (IgD)-secreting murine plasmacytomas occurs illegitimately. We demonstrate here that in human IgD-secreting myeloma cells freshly isolated from patient bone marrow and in normal peripheral blood B lymphocytes, an IgD switch can occur through homologous recombination of a direct repeat consisting of a 442-bp sequence 1.5 kbp 3' of the JH complex and a 443-bp sequence that is duplicated almost perfectly (96% similarity) 1.7 kbp 5' of the Cc, gene (442/443-base-pair [bp] repeat). This homologous recombination mechanism is not exclusive for IgD switching, since C^deletion endpoints in two established IgD-secreting myeloma cell lines fall outside the 442/443-bp repeat. The 442/443-bp mediated recombination shows cell type specificity, and we propose that it represents a unique mode for increased levels of IgD secretion in humans.The immunoglobulin heavy chain locus is located on chromosome 14 in humans. A heavy chain variable region (VH) gene is composed of one member from each of three gene families designated variable (V), diversity (D), and joining (J). The heavy chain constant region (CH) genes are located downstream of these VH genes in the order C t-CS-Cy3-cyl-C+£-Cal-CyC-y2-cy4-Ce,C.2 (3,12,25). In the primary immune response, the VH gene is transcribed along with the nearest downstream constant region gene, C, , to form a ,u heavy chain mRNA (50). During further B-cell differentiation, however, a given B cell and its progeny may shift from the production of immunoglobulin M (IgM) to one of the other heavy chain isotypes by the expression of downstream CH genes (reviewed in references 28 and 53). Studies primarily with myelomas have indicated that the switch phenomenon is most often the result of an intrachromosomal rearrangement between switch site (S) sequences located upstream of the heavy chain genes. Upon switching, the assembled VDJ gene is brought adjacent to the heavy chain gene to be expressed, resulting in the deletion of the intervening CH genes. Studies, at the DNA sequence level, of mice and humans have demonstrated that these S regions consist of 2 to 10 kilobases (kb) of tandem arrays of repeated sequences (8, 12, 20, 34-36, 41, 42, 48, 56-58). This description of the heavy chain class switch applies to all antibody classes except IgD. To date, the only biological function attributed to IgD with any certainty is serving as an antigen receptor along with IgM on the surface of virgin B cells (22,26,27,33 within the JH-C,, intron some 1.5 kbp 5' of S,, (30).To determine whether either of these sequences is implicated in the secretion of IgD, we have examined primary IgD-secreting myelomas from bone marrow, two established IgD-secreting myeloma cell lines, and normal B lymphocytes from peripheral blood. We found evidence for homologous recombination of the repeat co...

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Presence of serum IgD and IgD‐containing plasma cells in the mouse

Cited by 28 publications

References 15 publications

Biogenesis of membrane-bound and secreted immunoglobulins: two primary translation products of the human delta chain, differentially N-glycosylated to four discrete forms in vivo and in vitro.

Biogenesis of membrane-bound and secreted immunoglobulins: two primary translation products of the human delta chain, differentially N-glycosylated to four discrete forms in vivo and in vitro.

Illegitimate recombination generates a class switch from C mu to C delta in an IgD-secreting plasmacytoma.

Immunoglobulin D switching can occur through homologous recombination in human B cells.

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