Abstract
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.
Highlights
The regulation of offspring allergy development mediated by maternal immune status has already been shown by several groups [1,2,3,4]
Using a standardized murine model of allergy inhibition mediated by maternal immunization, in which the induction of B10 cells was demonstrated [7,8], we aimed to investigate whether the thymus can mature B10 cells, and to generate evidence regarding the potential of maternal immunization to modulate this process with a translational approach
We analyzed the phenotype of B cells during their maturation process in the two main primary lymphoid organs (PLOs), the thymus and the bone marrow, during the neonatal period
Summary
The regulation of offspring allergy development mediated by maternal immune status has already been shown by several groups [1,2,3,4]. B10 cells have subsequently been described as a regulatory population that play a pivotal role in inhibiting inflammation in several murine models [11,12,13,14,15,16] and participate in human immune regulation [17,18,19,20,21,22]. Together, these studies demonstrate the peripheral induction and functionality of B10 cells, but whether these cells can originate in PLOs or in which PLOs they can be generated has not been elucidated
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