IgG from Dermatophagoides pteronyssinus (Der p)-atopic individuals modulates non-atopic thymic B cell phenotype (alfa-4/beta-7) and cytokine production (IFN-γ, IL-9, and IL-10) with direct membrane interaction.

Studies about thymic B cells are scarce in the literature, but it was suggested that they can exert modulatory and regulatory functions on the immune system. Thymic B cells can play some role in regulating the most frequent allergic background worldwide, the atopy induced by the mite Dermatophagoides pteronyssinus (Der p). Here, we aimed to evaluate if the polyclonal IgG repertoire produced by Der p-atopic individuals can influence the homing and cytokine profile of human thymic B derived from non-atopic children aged less than seven days. With this purpose, we produced polyclonal IgG formulations and cultivated human thymocytes in their presence. We also assessed IgG subclasses and the direct interaction of IgG with thymic B cell membranes. Our results could demonstrate that Der p-atopic IgG could not reduce the expression of α4ß7 homing molecule as observed in response to the other IgG formulations and could reduce the frequency of IFN-γ- and IL-9-producing thymic B cells compared to the mock condition. Der p-atopic IgG could also induce thymic IL-10-producing B cells compared to control conditions. The IgG derived from Der p-atopic individuals failed to diminish the population of IL-13-producing thymic B cells, unlike the reduction observed with other IgG formulations when compared to the mock condition. All IgG formulations had similar levels of IgG subclasses and directly interacted with thymic B cell membranes. Finally, we performed experiments using peripheral non-atopic B cells where IgG effects were not observed. In conclusion, our observation demonstrates that IgG induced in allergic individuals can modulate non-atopic thymic B cells, potentially generating thymic B cells prone to allergy development, which seems to not occur in mature B cells.

Preconceptional immunization with an allergen inhibits offspring thymic Th17 cells maturation without influence on Th1 and Th2 cells.

The mechanisms through which maternal immunization can modulate offspring thymic maturation of lymphocytes are not fully understood. Here, we aimed to evaluate whether maternal OVA-immunization can inhibit the maturation of Th17 cells on offspring thymus. C57BL/6 females were immunized with OVA in Alum or Alum alone and mated with normal WT males. Offspring thymus was evaluated at three or 20 days of age. The demonstration that maternal OVA-immunization can inhibit offspring allergy development validated our experimental protocol. First, we observed that maternal OVA-immunization can inhibit the expression of R or γT and IL-17 molecules on immature T cells (CD4+CD8+) and TCD4 cells (CD4+CD8-) without interference on TCD8 cells (CD4-CD8+) on three-day-old offspring. A very similar effect could be observed on 20-day-old offspring. Additionally, a Th2 skewed profile could be found on the spleen of immunized pups from OVA-immunized mothers, but no influence was detected on offspring thymic Th1/Th2 profiles. Together, these data demonstrate that maternal immunization with an allergen can modulate offspring thymic maturation of Th17 cells without influencing Th1/Th2 patterns.