TGF-β1 induces germ-line transcripts of both IgA subclasses in human B lymphocytes

Islam, Khalid B.; Nilsson, Lars; Sideras, Paschalis; Hammarström, Lennart; Smith, C. I. Edvard

doi:10.1093/intimm/3.11.1099

Cited by 124 publications

(77 citation statements)

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“…TGF-b may be important in cartilage repair, as it can induce collagen synthesis [39]. At lower concentrations, TGF-b is a switch factor for immunoglobulin A (IgA) production [40][41][42] and it is necessary for production of all IgG subclasses in murine B cells [43] and for the induction of IgG2b production [24,31]. As high RF titres are a characteristic feature of RA, a potential pathogenic role for TGF-b might be to locally stimulate antibody production.…”

Section: Discussionmentioning

confidence: 99%

Synovial Fluid Cytokines in Patients with Rheumatoid Arthritus or Other Arthritic Lesions

Lettesjö¹,

Nordström²,

Ström³

et al. 1998

Scand J Immunol

103

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Section: Discussionmentioning

confidence: 99%

Synovial Fluid Cytokines in Patients with Rheumatoid Arthritus or Other Arthritic Lesions

Lettesjö¹,

Nordström²,

Ström³

et al. 1998

Scand J Immunol

103

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“…Moreover, the germ-line C71 transcript was amplified from cDNA of healthy controls by the addition of rIL-2 to PWM-stimulated PBMC or SAC-stimulated LCL, while it was not amplified from cDNA of the patient. Islam et al showed that In germ-line transcripts could be induced by transforming growth factor-beta 1 (TGF-/?I) [24]. In this study.…”

Section: Discussionmentioning

confidence: 57%

Failure of IgG production due to a defect in the opening of the chromatin structure of Iγ1 region in a patient with IgG and IgA deficiency

Kondo

Inoue

Kasahara

et al. 1995

Clinical and Experimental Immunology

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SUMMARYPatients with common variable immunodeficiency (CVID) display reduced levels of two or all three of the major immunoglobulin isotypes, and the deficiency is characterized by failure of B cells to differentiate into plasma cells in many cases. A patient (14 years old. female) showed normal serum IgM levels and low serum IgG and IgA levels, including low levels of all IgG sutjclasses. Northern blot analysis suggested that the patient's B cells may be defective at the immunoglobulin heavy chain isotype switch. The germ-line C7I transcript was amplified from cDNA of healthy controls by the addition of recombinant IL-2 (rIL-2) to pokeweed mitogen-stimulated peripheral mononuclear cells or Staphylococcus aureus Cowan I (SAC)-stimulated IgM-producing lymphoblastoid cell lines (LCL) transformed by Epstein-Barr virus, while it was not amplified from cDNA of the patient. In the I7I region of LCL cultured with SAC plus rIL-2, the inner cytosine in the 5' C-C-G-G 3' sequence nearest the 3' site of the I7I region, at least, was not completely unmethylated in the patient. Moreover, the DNase I hypersensitive site was not induced in the patient's LCL by SAC plus rIL-2. These results indicate that the defects of the immunoglobulin heavy chain isotype switch in the patient's B cells are due to failure in the synthesis of germ-line C7 transcripts, and this may be caused by defects in opening of the chromatin structures of specific switch regions.

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“…TGF-1 is produced by most cells and has an immunosuppressive effect in the immune system. It also induces germ-line transcripts of both IgA subclasses [22]. Studies on TGF-1 expression in CD4 + cells showed that there was an increase in IgAN patients [23,24].…”

Section: Introductionmentioning

confidence: 99%

Studies of the molecular basis of IgA production, subclass regulation and class-switch recombination in IgA nephropathy patients

Baskin

Pettersson²,

Rekola³

et al. 1996

Clinical and Experimental Immunology

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SUMMARYIgA nephropathy (IgAN), the most common form of glomerulonephritis, is characterized by normal to elevated levels of serum IgA. In order to understand the molecular mechanism(s) involved in the production of IgA in IgAN, peripheral blood mononuclear cells (PBMC) from these patients were analysed in this study. IL-10, transforming growth factor-beta 1 (TGF-¯1) and CD40 have previously been shown to be involved in IgA production. We show here that CD40L expression was increased three-fold in these patients. However, expression of TGF-¯1 in serum levels was comparable to controls. In vitro stimulation of PBMC with a polyclonal activator resulted in a three-fold increase in synthesis of both IgA subclasses, with a preference for IgA1 RNA. In situ hybridization studies also showed a three-fold increase in the numbers of IgA1-and IgA2-producing cells, but the subclass distribution was similar to the controls. Furthermore, using the nested primer polymerase chain reaction (PCR) for amplifying switch (S¹/S®) breakpoints we could demonstrate that in unstimulated PBMC the switch frequency did not differ from that of control donors. Sequence analysis of the amplified switch breakpoints and the I® regulatory region from patients showed no structural abnormality. Although we have previously demonstrated a correlation to in vivo germ-line RNA expression and class switching, no I® transcripts were detected in unstimulated PBMC from these patients. However, stimulation of PBMC with TGF-1 resulted in I® production. Taken together, results from in vivo and in vitro studies suggest that increased cytokine production and hyperresponsiveness to polyclonal stimulation may play an important role in the increased synthesis of IgA. The preference for IgA1 is due to increased production of IgA1 per cell, and the absence of I® RNA indicates that additional defect(s) in immune regulation may play an important role in the pathogenesis of IgAN.

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TGF-β1 induces germ-line transcripts of both IgA subclasses in human B lymphocytes

Cited by 124 publications

References 0 publications

Synovial Fluid Cytokines in Patients with Rheumatoid Arthritus or Other Arthritic Lesions

Synovial Fluid Cytokines in Patients with Rheumatoid Arthritus or Other Arthritic Lesions

Failure of IgG production due to a defect in the opening of the chromatin structure of Iγ1 region in a patient with IgG and IgA deficiency

Studies of the molecular basis of IgA production, subclass regulation and class-switch recombination in IgA nephropathy patients

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