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BAFF mediates splenic B cell response and antibody production in experimental Chagas disease.

Bermejo DA, Amezcua-Vesely MC, Montes CL, Merino MC, Gehrau RC, Cejas H, Acosta-Rodríguez EV, Gruppi A - PLoS Negl Trop Dis (2010)

Bottom Line: Acute infection results in polyclonal B cell activation associated with hypergammaglobulinemia, delayed specific humoral immunity and high levels of non-parasite specific antibodies.Interestingly, BAFF inhibition favors the parasitism in heart.Our results demonstrate, for the first time, an active role for BAFF in shaping the mature B cell repertoire in a parasite infection.

View Article: PubMed Central - PubMed

Affiliation: Department of Immunology, School of Chemical Sciences, National University of Córdoba, Córdoba, Argentina.

ABSTRACT

Background: B cells and antibodies are involved not only in controlling the spread of blood circulating Trypanosoma cruzi, but also in the autoreactive manifestations observed in Chagas disease. Acute infection results in polyclonal B cell activation associated with hypergammaglobulinemia, delayed specific humoral immunity and high levels of non-parasite specific antibodies. Since TNF superfamily B lymphocyte Stimulator (BAFF) mediates polyclonal B cell response in vitro triggered by T. cruzi antigens, and BAFF-Tg mice show similar signs to T. cruzi infected mice, we hypothesized that BAFF can mediate polyclonal B cell response in experimental Chagas disease.

Methodology/principal findings: BAFF is produced early and persists throughout the infection. To analyze BAFF role in experimental Chagas disease, Balb/c infected mice were injected with BR3:Fc, a soluble receptor of BAFF, to block BAFF activity. By BAFF blockade we observed that this cytokine mediates the mature B cell response and the production of non-parasite specific IgM and IgG. BAFF also influences the development of antinuclear IgG and parasite-specific IgM response, not affecting T. cruzi-specific IgG and parasitemia. Interestingly, BAFF inhibition favors the parasitism in heart.

Conclusions/significance: Our results demonstrate, for the first time, an active role for BAFF in shaping the mature B cell repertoire in a parasite infection.

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Related in: MedlinePlus

Immunoglobulin concentration in T. cruzi infected mice treated with BR3:Fc.Cells from spleen, lymph nodes, bone marrow and peritoneal cavity from T. cruzi infected (day 15 p.i.) mice treated with physiological solution (I) or BR3:Fc (I+BR3:Fc) or IgG2a control (I+IgG2a) were obtained and cultured with media without any stimulus for 30 h. IgM and IgG concentration (ng/ml) was determined in culture supernatants by ELISA. Diamonds represent the value obtained from each mouse. The lines represent the media value in each condition.*, p≤0.05. Results are representative for three individual experiments.
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pntd-0000679-g004: Immunoglobulin concentration in T. cruzi infected mice treated with BR3:Fc.Cells from spleen, lymph nodes, bone marrow and peritoneal cavity from T. cruzi infected (day 15 p.i.) mice treated with physiological solution (I) or BR3:Fc (I+BR3:Fc) or IgG2a control (I+IgG2a) were obtained and cultured with media without any stimulus for 30 h. IgM and IgG concentration (ng/ml) was determined in culture supernatants by ELISA. Diamonds represent the value obtained from each mouse. The lines represent the media value in each condition.*, p≤0.05. Results are representative for three individual experiments.

Mentions: The reduction of plasma cell number in T. cruzi infected mice treated with BR3:Fc correlated with a significant reduction in IgM and IgG concentration in culture supernatant of splenic cells (Fig 4). Interestingly, while the concentration of IgG was maintained, a reduction of IgM concentration was detected in the culture supernatant of cells from peritoneum of T. cruzi infected mice with blocked BAFF activity. According to plasma cell number results, no differences were detected in IgM and IgG concentrations produced by cells from lymph nodes and bone marrow from treated and untreated infected mice (Fig 4).


BAFF mediates splenic B cell response and antibody production in experimental Chagas disease.

Bermejo DA, Amezcua-Vesely MC, Montes CL, Merino MC, Gehrau RC, Cejas H, Acosta-Rodríguez EV, Gruppi A - PLoS Negl Trop Dis (2010)

Immunoglobulin concentration in T. cruzi infected mice treated with BR3:Fc.Cells from spleen, lymph nodes, bone marrow and peritoneal cavity from T. cruzi infected (day 15 p.i.) mice treated with physiological solution (I) or BR3:Fc (I+BR3:Fc) or IgG2a control (I+IgG2a) were obtained and cultured with media without any stimulus for 30 h. IgM and IgG concentration (ng/ml) was determined in culture supernatants by ELISA. Diamonds represent the value obtained from each mouse. The lines represent the media value in each condition.*, p≤0.05. Results are representative for three individual experiments.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2864296&req=5

pntd-0000679-g004: Immunoglobulin concentration in T. cruzi infected mice treated with BR3:Fc.Cells from spleen, lymph nodes, bone marrow and peritoneal cavity from T. cruzi infected (day 15 p.i.) mice treated with physiological solution (I) or BR3:Fc (I+BR3:Fc) or IgG2a control (I+IgG2a) were obtained and cultured with media without any stimulus for 30 h. IgM and IgG concentration (ng/ml) was determined in culture supernatants by ELISA. Diamonds represent the value obtained from each mouse. The lines represent the media value in each condition.*, p≤0.05. Results are representative for three individual experiments.
Mentions: The reduction of plasma cell number in T. cruzi infected mice treated with BR3:Fc correlated with a significant reduction in IgM and IgG concentration in culture supernatant of splenic cells (Fig 4). Interestingly, while the concentration of IgG was maintained, a reduction of IgM concentration was detected in the culture supernatant of cells from peritoneum of T. cruzi infected mice with blocked BAFF activity. According to plasma cell number results, no differences were detected in IgM and IgG concentrations produced by cells from lymph nodes and bone marrow from treated and untreated infected mice (Fig 4).

Bottom Line: Acute infection results in polyclonal B cell activation associated with hypergammaglobulinemia, delayed specific humoral immunity and high levels of non-parasite specific antibodies.Interestingly, BAFF inhibition favors the parasitism in heart.Our results demonstrate, for the first time, an active role for BAFF in shaping the mature B cell repertoire in a parasite infection.

View Article: PubMed Central - PubMed

Affiliation: Department of Immunology, School of Chemical Sciences, National University of Córdoba, Córdoba, Argentina.

ABSTRACT

Background: B cells and antibodies are involved not only in controlling the spread of blood circulating Trypanosoma cruzi, but also in the autoreactive manifestations observed in Chagas disease. Acute infection results in polyclonal B cell activation associated with hypergammaglobulinemia, delayed specific humoral immunity and high levels of non-parasite specific antibodies. Since TNF superfamily B lymphocyte Stimulator (BAFF) mediates polyclonal B cell response in vitro triggered by T. cruzi antigens, and BAFF-Tg mice show similar signs to T. cruzi infected mice, we hypothesized that BAFF can mediate polyclonal B cell response in experimental Chagas disease.

Methodology/principal findings: BAFF is produced early and persists throughout the infection. To analyze BAFF role in experimental Chagas disease, Balb/c infected mice were injected with BR3:Fc, a soluble receptor of BAFF, to block BAFF activity. By BAFF blockade we observed that this cytokine mediates the mature B cell response and the production of non-parasite specific IgM and IgG. BAFF also influences the development of antinuclear IgG and parasite-specific IgM response, not affecting T. cruzi-specific IgG and parasitemia. Interestingly, BAFF inhibition favors the parasitism in heart.

Conclusions/significance: Our results demonstrate, for the first time, an active role for BAFF in shaping the mature B cell repertoire in a parasite infection.

Show MeSH
Related in: MedlinePlus