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The strength of the antibody response to the nematode Ascaris lumbricoides inversely correlates with levels of B-Cell Activating Factor (BAFF).

Bornacelly A, Mercado D, Acevedo N, Caraballo L - BMC Immunol. (2014)

Bottom Line: Individuals with specific IgE levels to Ascaris >75th percentile had lower levels of soluble BAFF; those with specific IgG levels to Ascaris >75th percentile had reduced BAFF mRNA.Total IgE and specific IgE to mites were not related to BAFF levels.There was an inverse relationship between the cell-surface expression of BAFF-R on CD19+ B cells and BAFF levels at the transcriptional and protein level.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute for Immunological Research, University of Cartagena, Cra 5, #7-77, 13-0015 Cartagena, Colombia. lcaraballog@unicartagena.edu.co.

ABSTRACT

Background: B-Cell Activating Factor (BAFF) is a cytokine regulating antibody production. Polymorphisms in the gene encoding BAFF were associated with the antibody response to Ascaris but not to mite allergens. In the present study we evaluated the relationship between BAFF and specific antibodies against Ascaris and mites in 448 controls and 448 asthmatics. Soluble BAFF was measured by ELISA and BAFF mRNA by qPCR. Surface expression of BAFF and its receptor (BAFF-R) was analyzed by flow cytometry.

Results: Individuals with specific IgE levels to Ascaris >75th percentile had lower levels of soluble BAFF; those with specific IgG levels to Ascaris >75th percentile had reduced BAFF mRNA. Total IgE and specific IgE to mites were not related to BAFF levels. There were no differences in soluble BAFF or mRNA levels between asthmatics and controls. There was an inverse relationship between the cell-surface expression of BAFF-R on CD19+ B cells and BAFF levels at the transcriptional and protein level.

Conclusions: These findings suggest that differences in BAFF levels are related to the strength of the antibody response to Ascaris.

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Related in: MedlinePlus

Cell surface expression of BAFF and BAFF-R in PBMC, monocytes and B cells. A. Cell surface expression of BAFF and BAFF-R on gated monocytes (CD14+) and B cells (CD19+). A representative example out of 113 PBMCs samples tested. IKO: isotype control B. Cell surface expression of BAFF and BAFF-R in purified monocytes C. Cell surface expression of BAFF and BAFF-R in purified B cells.
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Figure 4: Cell surface expression of BAFF and BAFF-R in PBMC, monocytes and B cells. A. Cell surface expression of BAFF and BAFF-R on gated monocytes (CD14+) and B cells (CD19+). A representative example out of 113 PBMCs samples tested. IKO: isotype control B. Cell surface expression of BAFF and BAFF-R in purified monocytes C. Cell surface expression of BAFF and BAFF-R in purified B cells.

Mentions: Since there were previous reports showing an inverse relationship between BAFF and BAFF receptor[50,52,53], the expression of membrane-bound BAFF and BAFF-R was evaluated on PBMCs (n = 113). We did not detect cell surface expression of BAFF in gated CD14+ cells (monocytes), lymphocytes or gated CD19+ cells (B cells); and, as previously described[54], the BAFF-R was highly expressed in peripheral B cells but not in monocytes (Figure 4A). Similar findings were obtained when cell-surface expression of BAFF and BAFF-R were analyzed in sorted monocytes (Figure 4B) and B cells (Figure 4C) from six non-asthmatic controls. As expected[54] we found that plasmablasts (CD27high, CD38high), switched-memory B cells, mature naïve B cells and transitional B cells expressed BAFF receptor (Additional file1). The relationship between the cell-surface expression of BAFF-receptor (BAFF-R) on CD19+ B cells (median fluorescence intensity, MFI) with the soluble BAFF levels and the BAFF mRNA levels in PBMCs was evaluated in the subgroup of 113 individuals with flow cytometry data. These observations had a normal distribution in this dataset and therefore parametric tests (Pearson’s correlation) were used (Additional file2). We found a significant inverse correlation between BAFF1 mRNA and the cell surface expression of BAFF-R in CD19+ B cells (r = - 0.23, p = 0.01), Figure 5A. This finding was independent of age, gender, disease status and the proportion of monocytes in the sample as tested in a linear regression model. However, no correlation was found with BAFF2 mRNA levels (r = - 0.13, p = 0.1). Regarding protein levels, we found an inverse correlation between soluble BAFF levels and the cell surface expression of BAFF-R in CD19+ B cells (r = -0.27, p = 0.003) Figure 5B. These observations were significant after adjustment by age, gender, disease status and the proportion of monocytes in the sample. The inverse relation between soluble BAFF levels and the cell surface expression of BAFF-R has been previously reported in mice and patients with deficiency of BAFF-R[50], patients with systemic lupus erythematous and Sjogren’s syndrome[52] hyper-IgE syndrome[53] and acute malaria[37]. In this model, the 8.2% of the variance in BAFF-R expression can be explained by the soluble BAFF levels. In the context of immune responses to Ascaris, it remains to be elucidated how this BAFF/BAFF-R axis is related to the synthesis of specific antibody levels.


The strength of the antibody response to the nematode Ascaris lumbricoides inversely correlates with levels of B-Cell Activating Factor (BAFF).

Bornacelly A, Mercado D, Acevedo N, Caraballo L - BMC Immunol. (2014)

Cell surface expression of BAFF and BAFF-R in PBMC, monocytes and B cells. A. Cell surface expression of BAFF and BAFF-R on gated monocytes (CD14+) and B cells (CD19+). A representative example out of 113 PBMCs samples tested. IKO: isotype control B. Cell surface expression of BAFF and BAFF-R in purified monocytes C. Cell surface expression of BAFF and BAFF-R in purified B cells.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4067067&req=5

Figure 4: Cell surface expression of BAFF and BAFF-R in PBMC, monocytes and B cells. A. Cell surface expression of BAFF and BAFF-R on gated monocytes (CD14+) and B cells (CD19+). A representative example out of 113 PBMCs samples tested. IKO: isotype control B. Cell surface expression of BAFF and BAFF-R in purified monocytes C. Cell surface expression of BAFF and BAFF-R in purified B cells.
Mentions: Since there were previous reports showing an inverse relationship between BAFF and BAFF receptor[50,52,53], the expression of membrane-bound BAFF and BAFF-R was evaluated on PBMCs (n = 113). We did not detect cell surface expression of BAFF in gated CD14+ cells (monocytes), lymphocytes or gated CD19+ cells (B cells); and, as previously described[54], the BAFF-R was highly expressed in peripheral B cells but not in monocytes (Figure 4A). Similar findings were obtained when cell-surface expression of BAFF and BAFF-R were analyzed in sorted monocytes (Figure 4B) and B cells (Figure 4C) from six non-asthmatic controls. As expected[54] we found that plasmablasts (CD27high, CD38high), switched-memory B cells, mature naïve B cells and transitional B cells expressed BAFF receptor (Additional file1). The relationship between the cell-surface expression of BAFF-receptor (BAFF-R) on CD19+ B cells (median fluorescence intensity, MFI) with the soluble BAFF levels and the BAFF mRNA levels in PBMCs was evaluated in the subgroup of 113 individuals with flow cytometry data. These observations had a normal distribution in this dataset and therefore parametric tests (Pearson’s correlation) were used (Additional file2). We found a significant inverse correlation between BAFF1 mRNA and the cell surface expression of BAFF-R in CD19+ B cells (r = - 0.23, p = 0.01), Figure 5A. This finding was independent of age, gender, disease status and the proportion of monocytes in the sample as tested in a linear regression model. However, no correlation was found with BAFF2 mRNA levels (r = - 0.13, p = 0.1). Regarding protein levels, we found an inverse correlation between soluble BAFF levels and the cell surface expression of BAFF-R in CD19+ B cells (r = -0.27, p = 0.003) Figure 5B. These observations were significant after adjustment by age, gender, disease status and the proportion of monocytes in the sample. The inverse relation between soluble BAFF levels and the cell surface expression of BAFF-R has been previously reported in mice and patients with deficiency of BAFF-R[50], patients with systemic lupus erythematous and Sjogren’s syndrome[52] hyper-IgE syndrome[53] and acute malaria[37]. In this model, the 8.2% of the variance in BAFF-R expression can be explained by the soluble BAFF levels. In the context of immune responses to Ascaris, it remains to be elucidated how this BAFF/BAFF-R axis is related to the synthesis of specific antibody levels.

Bottom Line: Individuals with specific IgE levels to Ascaris >75th percentile had lower levels of soluble BAFF; those with specific IgG levels to Ascaris >75th percentile had reduced BAFF mRNA.Total IgE and specific IgE to mites were not related to BAFF levels.There was an inverse relationship between the cell-surface expression of BAFF-R on CD19+ B cells and BAFF levels at the transcriptional and protein level.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute for Immunological Research, University of Cartagena, Cra 5, #7-77, 13-0015 Cartagena, Colombia. lcaraballog@unicartagena.edu.co.

ABSTRACT

Background: B-Cell Activating Factor (BAFF) is a cytokine regulating antibody production. Polymorphisms in the gene encoding BAFF were associated with the antibody response to Ascaris but not to mite allergens. In the present study we evaluated the relationship between BAFF and specific antibodies against Ascaris and mites in 448 controls and 448 asthmatics. Soluble BAFF was measured by ELISA and BAFF mRNA by qPCR. Surface expression of BAFF and its receptor (BAFF-R) was analyzed by flow cytometry.

Results: Individuals with specific IgE levels to Ascaris >75th percentile had lower levels of soluble BAFF; those with specific IgG levels to Ascaris >75th percentile had reduced BAFF mRNA. Total IgE and specific IgE to mites were not related to BAFF levels. There were no differences in soluble BAFF or mRNA levels between asthmatics and controls. There was an inverse relationship between the cell-surface expression of BAFF-R on CD19+ B cells and BAFF levels at the transcriptional and protein level.

Conclusions: These findings suggest that differences in BAFF levels are related to the strength of the antibody response to Ascaris.

Show MeSH
Related in: MedlinePlus