BackgroundThe mechanisms through which allergies can be inhibited after preconception immunization with allergens are not fully understood. We aimed to evaluate whether maternal immunization can induce a regulatory B (B10) cell population in offspring in concert with allergy inhibition.MethodsC57BL/6 females were or were not immunized with OVA and were mated with normal WT males. Their offspring were evaluated at 3 days of age or 20 days after neonatal immunization. Human peripheral B cells from atopic and non-atopic individuals were also evaluated.ResultsPreconception OVA immunization induced B10 cells in offspring, and IL-10 production appeared to be critical for FcγRIIB upregulation in offspring B cells. Murine and human IL-10-producing B cells responded in vitro to IgG according to the atopic repertoire of the cells.ConclusionsOur results reveal that maternal immunization induces allergen-specific B10 cells in offspring and a pivotal role for the IgG repertoire in IL-10 production by murine and human B cells.Electronic supplementary materialThe online version of this article (doi:10.1186/s13223-017-0195-8) contains supplementary material, which is available to authorized users.

IgG of AD patients can stimulate cytokine production in infant thymocytes and thus resembles the peripheral profile observed in adults. These findings suggest a novel mechanism that can contribute to AD pathogenesis.

The regulatory effect of allergic responses induced by IgG antibodies on human intra-thymic cells has not been reported in the literature. The aim of this study was to evaluate the possible differential effect of purified IgG from atopic and non-atopic individuals on human intra-thymic αβT cell cytokine production. Thymic tissues were obtained from 14 patients who were less than 7 d old. Additionally, blood samples were collected from atopic and non-atopic volunteers. Thymocytes and peripheral blood mononuclear cells were cultured with purified atopic or non-atopic IgG, and intracellular cytokine production was assessed. Purified IgG did not influence the frequency or viability of human intra-thymic αβT cells. Purified non-atopic IgG induced greater IFN-γ production by intra-thymic CD4+CD8+ T cells than did the mock treatment and atopic IgG. A similar effect of purified non-atopic IgG on TCD8 cells was observed compared with the mock treatment. Atopic IgG inhibited IFN-γ and TGF-β production by intra-thymic TCD4 cells. Treatment with intravenous immunoglobulin resulted in intermediate levels of IFN-γ and TGF-β in intra-thymic TCD4 cells compared with treatment with atopic and non-atopic IgG. Peripheral TCD4 cells from non-atopic individuals produced IFN-γ only in response to atopic IgG. This report describes novel evidence revealing that IgG from atopic individuals may influence intracellular IFN-γ production by intra-thymic αβT cells in a manner that may favor allergy development.

Background Atopic dermatitis (AD) pathogenesis still needs to be elucidated, but invariant natural killer T (iNKT) cell involvement was already described by several groups. Our group has demonstrated that IgG antibodies purified from AD patients can modulate cytokine production by thymic T cells. Here we aimed to investigate if IgG from AD patients can modulate infant non-atopic thymic iNKT cells cytokine production in order to collaborate with the elucidation of AD development in infancy.Methods Thymic tissues were obtained from children from non-atopic mothers, and IgG was purified from AD patients diagnosed as moderate or severe and, as controls, from subjects clinically classified as non-atopic individuals. PBMCs from non-atopic individuals were also used in this study. ResultsOur results demonstrated that IgG from AD patients could induce non-atopic children thymic iNKT cells to produce higher levels of intracellular IL-4, IL-10, and IL-17 when compared to all control conditions. No effect was observed in non-atopic adults peripheral iNKT. We also observed that IgG from AD patients induces an increase in the expression of CD4 and Rorct transcription factor in non-atopic children thymic iNKT cells compared to the condition of all controls.Conclusions These observations suggest that IgG from AD patients can induce a cytokine profile by thymic iNKT cells from non-atopic infants compatible with the observations in AD development, which can collaborate with the elucidation of AD pathogenesis.

No abstract