Spontaneous production of granulocyte colony-stimulating factor in vitro by human B-lineage lymphocytes is a distinctive marker of germinal center cells

Anna Corcione, Lucia Baldi, Simona Zupo, Mariella Dono, Gabriella Biolcati Rinaldi, Silvio Roncella, Giuseppe Taborelli, Mauro Truini, Manlio Ferrarini, Vito Pistoia

Research output: Contribution to journalArticle

Abstract

The ability of human B lymphocytes to produce granulocyte (G)-CSF in vitro was investigated. Highly purified tonsillar B cells were fractionated into large and small cells by a Percoll density gradient, cultured, and tested for G-CSF gene expression. Large B cells spontaneously produced G-CSF mRNA and protein, whereas small B cells did not, even after incubation with various stimuli. Immunophenotypic analyses showed that large B lymphocytes contained approximately 60 to 70% of cells with the characteristic surface markers of germinal center (GC) B cells (CD38+, CD10+, and surface IgG+). The remaining cells expressed CD39, CD23, and surface IgD and were presumably in vivo-activated follicular mantle zone B cells. Fractionation of the large B lymphocytes into CD39+, surface IgD+, and CD39-, surface IgD- cells showed that the latter, but not the former, cell type produced G-CSF spontaneously in culture. Stimulation of purified (CD39-, surface IgD-) GC B cells with a CD40 mAb alone or in combination with IL-4 increased G-CSF production. Because these stimuli rescued a large fraction of GC cells (up to 50%) from spontaneous apoptosis in vitro, the finding may suggest that prevention of apoptotic death resulted in an increased G-CSF production or that CD40 mab and/or IL-4 increased G-CSF gene expression in G-CSF-producing GC B cells. Malignant B cells purified from the invaded lymph nodes of three patients with follicular center cell lymphoma and three Burkitt lymphoma cell lines, which had an immunophenotype identical with that of normal GC B cells, spontaneously produced G-CSF in vitro, thus confirming the GC origin of the cytokine. Incubation of normal purified GC B cells with rG-CSF resulted in the rescue of GC B cells from apoptosis, suggesting that G-CSF may be used by GC B cells in an autocrine manner. This autocrine loop of production and response to G-CSF by GC B cells may be activated by stimuli such as those delivered via the surface CD40 molecule, that participate in the rescue of GC B cells from apoptosis.

Original languageEnglish
Pages (from-to)2868-2877
Number of pages10
JournalJournal of Immunology
Volume153
Issue number7
Publication statusPublished - Oct 1 1994

Fingerprint

Germinal Center
Granulocyte Colony-Stimulating Factor
B-Lymphocytes
Lymphocytes
Immunoglobulin D
In Vitro Techniques
Apoptosis
Interleukin-4
Gene Expression
Burkitt Lymphoma

ASJC Scopus subject areas

  • Immunology

Cite this

Spontaneous production of granulocyte colony-stimulating factor in vitro by human B-lineage lymphocytes is a distinctive marker of germinal center cells. / Corcione, Anna; Baldi, Lucia; Zupo, Simona; Dono, Mariella; Rinaldi, Gabriella Biolcati; Roncella, Silvio; Taborelli, Giuseppe; Truini, Mauro; Ferrarini, Manlio; Pistoia, Vito.

In: Journal of Immunology, Vol. 153, No. 7, 01.10.1994, p. 2868-2877.

Research output: Contribution to journalArticle

Corcione, A, Baldi, L, Zupo, S, Dono, M, Rinaldi, GB, Roncella, S, Taborelli, G, Truini, M, Ferrarini, M & Pistoia, V 1994, 'Spontaneous production of granulocyte colony-stimulating factor in vitro by human B-lineage lymphocytes is a distinctive marker of germinal center cells', Journal of Immunology, vol. 153, no. 7, pp. 2868-2877.
Corcione, Anna ; Baldi, Lucia ; Zupo, Simona ; Dono, Mariella ; Rinaldi, Gabriella Biolcati ; Roncella, Silvio ; Taborelli, Giuseppe ; Truini, Mauro ; Ferrarini, Manlio ; Pistoia, Vito. / Spontaneous production of granulocyte colony-stimulating factor in vitro by human B-lineage lymphocytes is a distinctive marker of germinal center cells. In: Journal of Immunology. 1994 ; Vol. 153, No. 7. pp. 2868-2877.
@article{23e4bd411c144fe38057fea546cf05ee,
title = "Spontaneous production of granulocyte colony-stimulating factor in vitro by human B-lineage lymphocytes is a distinctive marker of germinal center cells",
abstract = "The ability of human B lymphocytes to produce granulocyte (G)-CSF in vitro was investigated. Highly purified tonsillar B cells were fractionated into large and small cells by a Percoll density gradient, cultured, and tested for G-CSF gene expression. Large B cells spontaneously produced G-CSF mRNA and protein, whereas small B cells did not, even after incubation with various stimuli. Immunophenotypic analyses showed that large B lymphocytes contained approximately 60 to 70{\%} of cells with the characteristic surface markers of germinal center (GC) B cells (CD38+, CD10+, and surface IgG+). The remaining cells expressed CD39, CD23, and surface IgD and were presumably in vivo-activated follicular mantle zone B cells. Fractionation of the large B lymphocytes into CD39+, surface IgD+, and CD39-, surface IgD- cells showed that the latter, but not the former, cell type produced G-CSF spontaneously in culture. Stimulation of purified (CD39-, surface IgD-) GC B cells with a CD40 mAb alone or in combination with IL-4 increased G-CSF production. Because these stimuli rescued a large fraction of GC cells (up to 50{\%}) from spontaneous apoptosis in vitro, the finding may suggest that prevention of apoptotic death resulted in an increased G-CSF production or that CD40 mab and/or IL-4 increased G-CSF gene expression in G-CSF-producing GC B cells. Malignant B cells purified from the invaded lymph nodes of three patients with follicular center cell lymphoma and three Burkitt lymphoma cell lines, which had an immunophenotype identical with that of normal GC B cells, spontaneously produced G-CSF in vitro, thus confirming the GC origin of the cytokine. Incubation of normal purified GC B cells with rG-CSF resulted in the rescue of GC B cells from apoptosis, suggesting that G-CSF may be used by GC B cells in an autocrine manner. This autocrine loop of production and response to G-CSF by GC B cells may be activated by stimuli such as those delivered via the surface CD40 molecule, that participate in the rescue of GC B cells from apoptosis.",
author = "Anna Corcione and Lucia Baldi and Simona Zupo and Mariella Dono and Rinaldi, {Gabriella Biolcati} and Silvio Roncella and Giuseppe Taborelli and Mauro Truini and Manlio Ferrarini and Vito Pistoia",
year = "1994",
month = "10",
day = "1",
language = "English",
volume = "153",
pages = "2868--2877",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "7",

}

TY - JOUR

T1 - Spontaneous production of granulocyte colony-stimulating factor in vitro by human B-lineage lymphocytes is a distinctive marker of germinal center cells

AU - Corcione, Anna

AU - Baldi, Lucia

AU - Zupo, Simona

AU - Dono, Mariella

AU - Rinaldi, Gabriella Biolcati

AU - Roncella, Silvio

AU - Taborelli, Giuseppe

AU - Truini, Mauro

AU - Ferrarini, Manlio

AU - Pistoia, Vito

PY - 1994/10/1

Y1 - 1994/10/1

N2 - The ability of human B lymphocytes to produce granulocyte (G)-CSF in vitro was investigated. Highly purified tonsillar B cells were fractionated into large and small cells by a Percoll density gradient, cultured, and tested for G-CSF gene expression. Large B cells spontaneously produced G-CSF mRNA and protein, whereas small B cells did not, even after incubation with various stimuli. Immunophenotypic analyses showed that large B lymphocytes contained approximately 60 to 70% of cells with the characteristic surface markers of germinal center (GC) B cells (CD38+, CD10+, and surface IgG+). The remaining cells expressed CD39, CD23, and surface IgD and were presumably in vivo-activated follicular mantle zone B cells. Fractionation of the large B lymphocytes into CD39+, surface IgD+, and CD39-, surface IgD- cells showed that the latter, but not the former, cell type produced G-CSF spontaneously in culture. Stimulation of purified (CD39-, surface IgD-) GC B cells with a CD40 mAb alone or in combination with IL-4 increased G-CSF production. Because these stimuli rescued a large fraction of GC cells (up to 50%) from spontaneous apoptosis in vitro, the finding may suggest that prevention of apoptotic death resulted in an increased G-CSF production or that CD40 mab and/or IL-4 increased G-CSF gene expression in G-CSF-producing GC B cells. Malignant B cells purified from the invaded lymph nodes of three patients with follicular center cell lymphoma and three Burkitt lymphoma cell lines, which had an immunophenotype identical with that of normal GC B cells, spontaneously produced G-CSF in vitro, thus confirming the GC origin of the cytokine. Incubation of normal purified GC B cells with rG-CSF resulted in the rescue of GC B cells from apoptosis, suggesting that G-CSF may be used by GC B cells in an autocrine manner. This autocrine loop of production and response to G-CSF by GC B cells may be activated by stimuli such as those delivered via the surface CD40 molecule, that participate in the rescue of GC B cells from apoptosis.

AB - The ability of human B lymphocytes to produce granulocyte (G)-CSF in vitro was investigated. Highly purified tonsillar B cells were fractionated into large and small cells by a Percoll density gradient, cultured, and tested for G-CSF gene expression. Large B cells spontaneously produced G-CSF mRNA and protein, whereas small B cells did not, even after incubation with various stimuli. Immunophenotypic analyses showed that large B lymphocytes contained approximately 60 to 70% of cells with the characteristic surface markers of germinal center (GC) B cells (CD38+, CD10+, and surface IgG+). The remaining cells expressed CD39, CD23, and surface IgD and were presumably in vivo-activated follicular mantle zone B cells. Fractionation of the large B lymphocytes into CD39+, surface IgD+, and CD39-, surface IgD- cells showed that the latter, but not the former, cell type produced G-CSF spontaneously in culture. Stimulation of purified (CD39-, surface IgD-) GC B cells with a CD40 mAb alone or in combination with IL-4 increased G-CSF production. Because these stimuli rescued a large fraction of GC cells (up to 50%) from spontaneous apoptosis in vitro, the finding may suggest that prevention of apoptotic death resulted in an increased G-CSF production or that CD40 mab and/or IL-4 increased G-CSF gene expression in G-CSF-producing GC B cells. Malignant B cells purified from the invaded lymph nodes of three patients with follicular center cell lymphoma and three Burkitt lymphoma cell lines, which had an immunophenotype identical with that of normal GC B cells, spontaneously produced G-CSF in vitro, thus confirming the GC origin of the cytokine. Incubation of normal purified GC B cells with rG-CSF resulted in the rescue of GC B cells from apoptosis, suggesting that G-CSF may be used by GC B cells in an autocrine manner. This autocrine loop of production and response to G-CSF by GC B cells may be activated by stimuli such as those delivered via the surface CD40 molecule, that participate in the rescue of GC B cells from apoptosis.

UR - http://www.scopus.com/inward/record.url?scp=0028068409&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028068409&partnerID=8YFLogxK

M3 - Article

C2 - 7522243

AN - SCOPUS:0028068409

VL - 153

SP - 2868

EP - 2877

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 7

ER -