RESUMO

Regulatory B (B10) cells can control several inflammatory diseases, including allergies; however, the origin of peripheral B10 cells is not fully understood, and the involvement of primary lymphoid organs (PLOs) as a primary site of maturation is not known. Here, using a murine model of allergy inhibition mediated by maternal immunization with ovalbumin (OVA), we aimed to evaluate whether B10 cells can mature in the thymus and whether IgG can mediate this process. Female mice were immunized with OVA, and offspring thymus, bone marrow, spleen, lung, and serum samples were evaluated at different times and after passive transfer of purified IgG or thymocytes. A translational approach was implemented using human nonatopic thymus samples, nonatopic peripheral blood mononuclear cells (PBMCs), and IgG from atopic or nonatopic individuals. Based on the expression of CD1d on B cells during maturation stages, we suggest that B10 cells can also mature in the murine thymus. Murine thymic B10 cells can be induced in vitro and in vivo by IgG and be detected in the spleen and lungs in response to an allergen challenge. Like IgG from atopic individuals, human IgG from nonatopic individuals can induce B10 cells in the infant thymus and adult PBMCs. Our observations suggest that B10 cells may mature in the thymus and that this mechanism may be mediated by IgG in both humans and mice. These observations may support the future development of IgG-based immunoregulatory therapeutic strategies.

Assuntos

Linfócitos B/imunologia , Imunoglobulina G/metabolismo , Interleucina-10/metabolismo , Adulto , Animais , Modelos Animais de Doenças , Feminino , Humanos , Camundongos , Projetos Piloto

RESUMO

BACKGROUND: The 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. METHODS: C57BL/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. RESULTS: Preconception 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. CONCLUSIONS: Our 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.