The Potential of IgG to Induce Murine and Human Thymic Maturation of IL-10+ B Cells (B10) Revealed in a Pilot Study

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.

IgG from atopic individuals can mediate non atopic infant thymic and adult peripheral CD8 TC2 skewing without influence on TC17 or TC22 cells

“…As theoretically discussed in 2017 with the "MatIgG primary modulation theory" (35), the passive transference of maternal IgG can modulate offspring immunity when maternal IgG reaches offspring primary organs modulating the immunity development according to maternal atopic state. This hypothesis has been confirmed with pieces of evidence obtained in murine (36,37) and translational experimental approaches (38,39).…”

Non-atopic Neonatal Thymic Innate Lymphoid Cell Subsets (ILC1, ILC2, and ILC3) Identification and the Modulatory Effect of IgG From Dermatophagoides Pteronyssinus (Derp)-Atopic Individuals

“…Apart from that, in the past years, some studies have demonstrated that IgG can play a pivotal role in mediating complex interactions that result in functional lymphocyte modulation during maturation in self or offspring primary lymphoid organs and how this implicates in the context of allergy (33,37,(49)(50)(51). These studies proposed several IgG idiotypes interacting with molecules expressed on B-and T-cell membranes during the maturation process, including clonal receptors (BCRs and TCRs).…”

“…Previous studies in the literature demonstrated that IgG antibodies could interact with lymphocytes precursors in the murine and human thymus, modulating its cytokine production as recently revised (31). Together, these pieces of evidence suggest that atopic and non-atopic individuals' IgG repertoire can differentially modulate the maturation of thymic TCD4, TCD8, iNKT B, and γδT cells modulating or inhibiting the development of allergy (32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42). In those observations, it has become evident that IgG antibodies can interact with a wide range of clonal or conserved receptors expressed in several cell populations.…”

Preconceptional Immunization Can Modulate Offspring Intrathymic IL-17-Producing γδT Cells with Epigenetic Implications Mediated by microRNAs

“…To evaluate intracellular IL-17 production, we adopted a previously standardized protocol for spontaneous cytokine production analyses for intracellular cytokine staining [ 17 , 21 , 27 , 43 ]. Briefly, thymocytes were cultured for 24 h at 3 × 10 6 cells/mL in RPMI (Gibco—ThermoFisher, Waltham, MA, USA) supplemented with 10% heat-inactivated fetal clone (FCS-III, HyClone, Logan, UT, USA) sera without stimulus and in the presence of 10 µg/mL brefeldin A (Sigma, St Louis, MO, USA).…”

“…Some hypotheses discussed that maternal immunization with allergens could broadly modulate offspring intrathymic maturation of T cells [ 18 , 19 , 20 ] and had been experimentally evidenced for murine and human γδT, Treg and Breg cells [ 12 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 ]. However, no molecular pieces of evidence have been obtained to elucidate if this mechanism involves some epigenetic alterations on modulated cells.…”