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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

Parasite specific immunoglobulins in sera from T. cruzi infected mice treated with BR3:Fc.Sera from T. cruzi infected mice treated with physiological solution (I) or BR3:Fc (I+BR3:Fc) or IgG2a control (I+IgG2a) were obtained at day 15 p.i. and analyzed by ELISA to determine T. cruzi specific IgM and IgG Ab titers. Diamonds represent the value obtained from each mouse. The lines represent the media value in each case. *, p≤0.05. Results are representative for two individual experiments.
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pntd-0000679-g005: Parasite specific immunoglobulins in sera from T. cruzi infected mice treated with BR3:Fc.Sera from T. cruzi infected mice treated with physiological solution (I) or BR3:Fc (I+BR3:Fc) or IgG2a control (I+IgG2a) were obtained at day 15 p.i. and analyzed by ELISA to determine T. cruzi specific IgM and IgG Ab titers. Diamonds represent the value obtained from each mouse. The lines represent the media value in each case. *, p≤0.05. Results are representative for two individual experiments.

Mentions: To analyze the biological significance of the reduced Ab response observed in BR3:Fc treated T. cruzi infected mice, we evaluated the levels of parasite specific Abs in sera. We observed that preventing BAFF binding drastically diminished trypomastigotes T. cruzi-specific IgM titers while T. cruzi-specific IgG titers did not change (Fig 5). Parasite-specific Abs were practically undetectable in the culture supernatants of the lymphoid organs obtained from infected mice indicating a low frequency of T. cruzi antigen-specific B cells as reported [8], [9] and a high frequency of non-parasite specific Abs (data not shown).


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)

Parasite specific immunoglobulins in sera from T. cruzi infected mice treated with BR3:Fc.Sera from T. cruzi infected mice treated with physiological solution (I) or BR3:Fc (I+BR3:Fc) or IgG2a control (I+IgG2a) were obtained at day 15 p.i. and analyzed by ELISA to determine T. cruzi specific IgM and IgG Ab titers. Diamonds represent the value obtained from each mouse. The lines represent the media value in each case. *, p≤0.05. Results are representative for two individual experiments.
© Copyright Policy
Related In: Results  -  Collection

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

pntd-0000679-g005: Parasite specific immunoglobulins in sera from T. cruzi infected mice treated with BR3:Fc.Sera from T. cruzi infected mice treated with physiological solution (I) or BR3:Fc (I+BR3:Fc) or IgG2a control (I+IgG2a) were obtained at day 15 p.i. and analyzed by ELISA to determine T. cruzi specific IgM and IgG Ab titers. Diamonds represent the value obtained from each mouse. The lines represent the media value in each case. *, p≤0.05. Results are representative for two individual experiments.
Mentions: To analyze the biological significance of the reduced Ab response observed in BR3:Fc treated T. cruzi infected mice, we evaluated the levels of parasite specific Abs in sera. We observed that preventing BAFF binding drastically diminished trypomastigotes T. cruzi-specific IgM titers while T. cruzi-specific IgG titers did not change (Fig 5). Parasite-specific Abs were practically undetectable in the culture supernatants of the lymphoid organs obtained from infected mice indicating a low frequency of T. cruzi antigen-specific B cells as reported [8], [9] and a high frequency of non-parasite specific Abs (data not shown).

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