B Lymphocyte Hyperactivity in Families of Patients with Systemic Lupus Erythematosus

Clark, J P; Bourne, Tim; Salaman, Myer R.; Seifert, Martin; Isenberg, David

doi:10.1006/jaut.1996.0008

Cited by 22 publications

(27 citation statements)

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“…conform to the general rule that IgM levels are higher in women than in men (9). Although no significant correlation was observed between patients and their relatives with respect to levels of NKT cells, IgG, or IgM, correlation coefficients were positive in each case, suggesting a degree of familial influence.…”

Section: Association Of Igg and Nkt Cells In Patients With Sle And Thsupporting

confidence: 54%

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Natural killer T cells in families of patients with systemic lupus erythematosus: Their possible role in regulation of IGG production

Green¹,

Kennell²,

Larché³

et al. 2007

Arthritis & Rheumatism

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Objective. To determine whether there is a link between the frequency of natural killer T (NKT) cells and high levels of IgG in patients with systemic lupus erythematosus (SLE) and their relatives.Methods. Blood samples were obtained from patients with SLE, their first-degree relatives, patients with rheumatoid arthritis (RA), and healthy control subjects. The frequency of NKT cells (defined as CD56؉ T cells) was expressed as a percentage of total blood lymphocytes. Plasma levels of total IgG and IgM, and IgG antibodies to double-stranded DNA (dsDNA) were determined.Results. The frequency of NKT cells was lower in patients with SLE than in control subjects. No such decrease was observed in the relatives of patients with SLE or in patients with RA. High levels of IgG were observed in both patients with SLE and their relatives, while low levels of IgM were observed in these same groups. In relatives of patients with SLE, an inverse correlation between the frequency of NKT cells and IgG levels was observed. Moreover, raised levels of IgG in patients with SLE and their relatives and high levels of IgG anti-dsDNA in patients were associated with low frequencies of NKT cells. Conclusion.These results suggest that NKT cells have an important role in the regulation of IgG production, although NKT cells with invariant T cell receptors may not necessarily be involved. NKT cells in the setting of SLE could lack the cytokine stimulus from NK or other cells that is needed to exert control on IgG production. Enhancement of NKT cell activity may provide a novel basis for therapy in SLE.

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Section: Association Of Igg and Nkt Cells In Patients With Sle And Thsupporting

confidence: 54%

“…The enzyme-linked immunosorbent assay (ELISA) procedures that were followed have been described previously (9). Flat-bottomed 96-well microtiter plates (M29AR; Sterilin, Feltham, UK) were coated with antiglobulin reagents or calf thymus dsDNA.…”

Section: Methodsmentioning

confidence: 99%

Natural killer T cells in families of patients with systemic lupus erythematosus: Their possible role in regulation of IGG production

Green¹,

Kennell²,

Larché³

et al. 2007

Arthritis & Rheumatism

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“…Counts effected following removal of beads from CD19 þ preparations of normal or SLE cells with 'detachabead' antibody (Dynal) confirmed a mean negative:positive cell yield ratio of about 10 (range [5][6][7][8][9][10][11][12][13][14][15]. Flow cytometry (see below) indicated that the fractionation procedure removed Ϸ 80% of B cells, providing a preparation of high purity (> 96%).…”

Section: Magnetic-bead Cell Fractionationmentioning

confidence: 99%

“…Culture supernatants were assayed for IgG and IgM by ELISA [11]. Supernatants were tested at four doubling dilutions starting at 1 in 2·5.…”

Section: Determination Of Total Igg and Igmmentioning

confidence: 99%

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Spontaneous immunoglobulin-producing capacity of cultures from lupus patients and normal donors following depletion of cells expressing CD19 or CD38

Bourne¹,

Zukowska-Cooper²,

Salaman³

et al. 1998

Clinical and Experimental Immunology

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SUMMARYCells spontaneously secreting IgG or IgM (ISC) are present at a high level in the blood of patients with systemic lupus erythematosus (SLE). By use of magnetic-bead techniques, mononuclear cells from such patients and healthy donors were fractionated according to expression of CD19 or CD38 and the cell fractions were then cultured in the absence of added mitogen/antigen for 5/6 days. Supernatant IgG and IgM were determined and, in addition, in the CD38 experiments ISC were enumerated both before and after culture. Much of the immunoglobulin-producing capacity of unfractionated cells (UFC) from both donor groups was recovered in the CD19 ¹ fraction, and no immunoglobulin was produced by CD19 þ cells suggesting, unexpectedly, that ISC were not expressing CD19. By contrast, CD38 fractionation resulted in nearly all ISC passing to the CD38 þ fraction which produced levels of immunoglobulin approaching 50% that of UFC. On culture of CD38 ¹ cells there was a build up in the number of IgG and IgM ISC, this being particularly striking in the controls with numbers well in excess of those in UFC. Not all these new ISC became CD38 þ , but the maturation process was more efficient in the SLE patients. The possibility is discussed that the spontaneous response in the CD38 ¹ populations is due to removal of CD38 þ natural killer (NK) cells. Removal of ISC that are present preculture is a helpful initial step in studying ISC generation in the disease.

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Bcl-2 leads to expression of anti-DNA B cells but no nephritis: a model for a clinical subset

et al. 1999

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Transgenic mice expressing anti‐DNA antibodies have been extensively studied as a model for understanding B cell regulation in systemic lupus erythematosus (SLE). BALB / c mice transgenic for the R4A‐γ2b heavy chain of an anti‐double‐stranded DNA (dsDNA) antibody produce two populations of high‐affinity anti‐dsDNA B cells, one deleted, and the other anergized. We generated double‐transgenic BALB / c mice expressing both the R4A‐γ2b heavy chain and the anti‐apoptotic bcl‐2 gene in the B cell compartment to study whether bcl‐2 overexpression differentially affected anergic and deleted B cells. The double‐transgenic mice (R4A / bcl‐2) express elevated serum titers of both high‐ and low‐affinity anti‐dsDNA antibodies and display rescue of autoreactive B cells that are normally either deleted or anergized. Despite the presence of anti‐dsDNA antibodies in their serum, R4A / bcl‐2‐transgenic mice do not develop nephritis, demonstrating that overexpression of bcl‐2 is not by itself sufficient to allow disease progression. This phenotype resembles that of some SLE patients who have high titers of anti‐DNA antibodies without nephritis.

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B Lymphocyte Hyperactivity in Families of Patients with Systemic Lupus Erythematosus

Cited by 22 publications

References 0 publications

Natural killer T cells in families of patients with systemic lupus erythematosus: Their possible role in regulation of IGG production

Natural killer T cells in families of patients with systemic lupus erythematosus: Their possible role in regulation of IGG production

Spontaneous immunoglobulin-producing capacity of cultures from lupus patients and normal donors following depletion of cells expressing CD19 or CD38

Bcl-2 leads to expression of anti-DNA B cells but no nephritis: a model for a clinical subset

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