IgD and B Cell Differentiation

Vitetta, Ellen S.; Uhr, Jonathan W.

doi:10.1111/j.1600-065x.1977.tb00245.x

Cited by 115 publications

(37 citation statements)

References 79 publications

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“…These results are consistent with the reports of other investigators that surface IgD, in contrast to surface IgM, is extremely susceptible to proteolysis (30,31 The phenomenon of loss of surface IgD from B cells has been described by several investigators to occur after stimulation of mature B cells by mitogens or antigens and is presumably the result of differentiation of B cells, which later become IgM-, IgG-, and IgA-secreting cells (20). In several recent studies, researchers have shown that spleen lymphocytes in NZB mice have markedly decreased levels of surface IgD relative to IgM (3,4,33).…”

Section: Discussionsupporting

confidence: 93%

Relationship between reduced b cell susceptibility to igm antibodies and reduced igd‐bearing b cells in patients with systemic lupus erythematosus

Suzuki

Sakurami²,

Imura

1982

Arthritis & Rheumatism

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Peripheral blood lymphocytes from 14 patients with systemic lupus erythematosus, 5 patients with rheumatoid arthritis, and 10 normal subjects were cultured for 7 days with or without anti‐IgM or anti‐IgD antibodies, and IgG‐ and IgM‐secreting cells were assayed by reverse hemolytic plaque assay. Surface immunoglobulin (Ig) isotypes on peripheral blood B cells were also examined by a direct anti‐Ig resetting reaction. In normal subjects and rheumatoid arthritis patients, the spontaneous development of IgG‐ and IgM‐secreting cells was markedly suppressed by anti‐IgM or anti‐IgD antibodies. Over 50% of peripheral blood B cells were IgD‐ and/or IgM‐bearing cells in normal subjects and in most patients with rheumatoid arthritis. In lupus patients, however, the suppression of IgG and IgM production by anti‐IgM or anti‐IgD antibodies was remarkably reduced, especially in the active stage. Furthermore, the percentage of IgD‐bearing cells in peripheral blood B cells was remarkably reduced, especially in patients with active disease. There was a good correlation between reduced susceptibility of B cells to anti‐IgM antibody‐mediated suppression and reduced percentage of IgD‐bearing cells in lupus patients.

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Section: Discussionsupporting

confidence: 93%

Relationship between reduced b cell susceptibility to igm antibodies and reduced igd‐bearing b cells in patients with systemic lupus erythematosus

Suzuki

Sakurami²,

Imura

1982

Arthritis & Rheumatism

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“…They first express only IgM as antigen receptor on their surface. When leaving the bone marrow as mature B cells, they coexpress a second antigen receptor, IgD, of the same specificity as IgM (1)(2)(3). Naive B cells and B cells located in primary follicles express both IgD and IgM, whereas splenic marginal-zone B cells and a large proportion of memory B cells only express IgM (5,6).…”

mentioning

confidence: 99%

Immunoglobulin D-deficient mice can mount normal immune responses to thymus-independent and -dependent antigens.

Nitschke

Kosco

Köhler

et al. 1993

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

124

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To examine the in vivo function of IgD we generated mice deficient for IgD by gene targeting. The IgDmice show a reduced B-cell compartment with 30-50% less B cells in the spleen and lymph nodes but show a normal pre-B-cell compartment. The surface-IgD-B cells express two to three times more surface IgM than B cells ofcontrol animals. Serum concentrations of the immunoglobuln isotpes of IgDmice are almost normal, indicating that surface-IgD expression is not necessary for class switching of B cells. Immunization experiments showed that IgD-mice could respond well to thymus-dependent and -independent antigens. After immunization normal germinal centers developed in the IgD-mice. cells (7, 8). In vivo the functions attributed to the engagement of sIgD vary from the acquisition of resistance to tolerance induction (10-12) and the initiation ofthe B-cell response (13) to a role in B-cell memory (6,14,15). Some ofthese functions were studied by using chronic anti-IgD treatment from birth (16,17), by in vitro sorting of sIgD+ and sIgD-B cells (10,18,19), by enzymatic removal of sIgD in vitro (11), or by transgenic mouse models (20). Discrepancies of results were found in these studies that could be generated by the nature of the indirect experimental systems used. Roes and Rajewsky (21) PCR and Southern Blots. ES cell clones were picked and prepared for a nested primer PCR analysis, as described (35). Genomic DNA for Southern blotting was prepared from ES cells or from the tail ends of mice.Flow Cytometric Analysis (FCM). FCM of single-cell suspensions of lymphatic organs was done on a FACScan flow cytometer (Becton Dickinson). The antibodies used for staining were either (i) biotinylated and counterstained with streptavidin-phycoerythrin 11-26C (anti-IgD, from J. Kearney, University of Alabama, Birmingham) ( Fig. 2 a and b), M41 (anti-IgM) (27) (Fig. 2 c and d), B7/6 (anti-IgM) (27) (Fig. 2 g and h) or (ii) conjugated with fluorescein isothiocyanate M41 (anti-IgM) (Fig. 2 a and

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“…This observation prompted much new research that led to the finding of an IgD homologue on B cells in many animals (13). Evidence is rapidly accumulating to support the idea that membrane IgD plays a key role in lymphocyte activation, differentiation, and proliferation (14).…”

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confidence: 99%

Structural studies of human IgD: Isolation by a two-step purification procedure and characterization by chemical and enzymatic fragmentation

Lin

Putnam

1979

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

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A myeloma IgD immunoglobulin (designated WAH) that was present in hig concentration in plasma (-3.5 g/dl) was purified in >90% yield by a two-step procedure of ammonium sulfate precipitation plus AcA 34 gel filtration. Although the plasma had been stored for 2 years without the addition of a proteolytic inhibitor, no "spontaneous" degradation was apparent and the isolated IgD remained structurally intact.However, the purified IgD showed extreme susceptibility in vitro to various proteolytic enzymes; e.g., Fabs (Mr % 47,000) and Fc (Mr -80,000) fragments were generated quantitatively after only 10 min of incubation with papain in the absence of cysteine. By combining limited enzymatic digestion, reductive cleavage, and cyanogen bromide fragmentation, several series of well defined fragments corresponding to the different regions and domains of the IgD molecule were generated. These fragments are useful for physical, chemical, and immunological studies, as well as for the sequence determination of the IgD 5 chain. A model of the IgD molecule was derived from such studies and from overlapping of the series-of fragments. The possible existence of an extra constant domain in the 5 chain appears unlikely in view of our finding of an extended hinge region of about 50 residues which can be cleaved off the amino terminus of the papain Fc by brief treatment with trypsin. In addition to a distinct stretch of carbohydrate attachment sites, the 5-chain hinge region contains a segment unusually rich in electrical charge. This charged segment is responsible for the lability of Igi to spontaneous degradation and may be related to its biological role as a B lymphocyte receptor. Although IgD was discovered as a fourth class of human immunoglobulins nearly 15 years ago (2, 3), detailed structural studies have previously been greatly hampered because of several unfavorable factors. First, the very low incidence of IgD myeloma, the short survival time of the patients, and the comparatively low serum concentration of myeloma IgD all restricted the chance of collecting an IgD sample in sufficient quantity to complete the necessary work (4). Second, the notorious susceptibility of most IgD proteins to "spontaneous" degradation either in situ or during fractionation further reduced the availability of intact IgD (5, 6). Third, the earlier failure to demonstrate any significant biological function for IgD detracted from interest in it (7). Nevertheless, preliminary studies revealed some interesting structural features of IgD molecules (8, 9). Thus, IgD, especially its Fca region, is very rich in carbohydrate. Its heavy chain (b chain) has a molecular weight suggesting either a five-domain structure (10) or a four-domain structure with an "extended" hinge region (5). The presence in IgD of a single inter-heavy-chain disulfide bond also appears to be unique among human immunoglobulins (11).In 1973, IgD was demonstrated to be a major class of receptor immunoglobulins on human B lymphocytes despite its low serum concentration (12)...

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IgD and B Cell Differentiation

Cited by 115 publications

References 79 publications

Relationship between reduced b cell susceptibility to igm antibodies and reduced igd‐bearing b cells in patients with systemic lupus erythematosus

Relationship between reduced b cell susceptibility to igm antibodies and reduced igd‐bearing b cells in patients with systemic lupus erythematosus

Immunoglobulin D-deficient mice can mount normal immune responses to thymus-independent and -dependent antigens.

Structural studies of human IgD: Isolation by a two-step purification procedure and characterization by chemical and enzymatic fragmentation

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