Two day old Wistar rats were tube fed with 1 or 10 micrograms of a mouse IgG1 monoclonal anti-idiotypic (a-Id) antibody that was directed against an anti-Escherichia coli-K13 capsular polysaccharide antibody. A control group was given 10 micrograms of an unrelated control antibody. Six weeks after the administration of antibodies, the rats were intestinally colonised with an ovalbumin (OVA)-producing E. coli O6K13 strain. At 8 weeks of age, the male rats (first generation) and the offsprings of the female rats (second generation), were parenterally immunised with OVA and dead wild type E. coli O6K13, and the immune response was followed. In the rats of the first generation, there were no major differences between the groups in the immune response to the bacterium. However, the offspring of the neonatally a-Id administered rats had a profoundly affected immune response to the idiotypically connected antigen K13, but also to other antigens on the bacteria. Thus, a-Id treatment in the first generation gave, in the second generation, a greatly enhanced serum antibody response to the spatially related antigens OVA and O6 LPS, as well as to the idiotypically connected antigen K13. Concurrently, the in vitro spleen cell proliferative response to both OVA and the wild type bacterium was lowered. Overall, greater effects were seen with the higher dose of a-Id. In conclusion, our results demonstrate that by giving monoclonal antibodies idiotypically connected to a single bacterial component to neonatal rats, one profoundly influence the immune response also to other-spatially related-bacterial antigens in their offsprings.
2It is essential for early human life that immunological responses to developing embryos are 3 tightly regulated. An imbalance in the activation and regulation of the human complement 4 system occurs in pregnancy complications, such as pre-eclampsia and recurrent miscarriage. 5We hereby present the first full analysis of the expression and deposition of complement 6 molecules in human pre-implantation embryos. Thus far, immunological imbalance has been 7 considered in stages of pregnancy following implantation. We here show that complement 8 activation and deposition takes place on developing human embryos already at the pre-9 implantation stage. Using confocal microscopy, we observed deposition of activation products 10 such as C1q, C3 and C5 on healthy developing embryos, which highlights the need for strict 11 complement regulation. The early embryos express the complement membrane inhibitors 12 CD46, CD55 and CD59 and bind the soluble regulators C4bp and factor H. These findings 13show that complement targets human embryos, and indicate potential adverse pregnancy 14 outcomes, if regulation of activation fails. In addition, single-cell RNA sequencing of embryos 15 at oocyte, zygote, 4-cell and 8-cell stages showed expression of complement genes, e.g. C1s, 16C2, C3, C5, factor B and factor D. This shows that the embryonic cells themselves have the 17 capacity to express C3 and C5, which may become activated and function as mediators of 18 cellular signaling. The specific local embryonic expression of complement components, 19regulators, and deposition of activation products on the surface of embryos suggests that 20 complement has immunoregulatory functions and may impact cellular homeostasis and 21 differentiation at the earliest stage of human life. 22 23 Keywords 24Complement, embryo, development, pre-implantation 25 26 Statement of significance 27While canonical functions of the complement system relate to pathogen-defence, it is known 28 to drive certain immune pathologies. The work here described shows, for the first time, 29 expression and localization of a full range of complement molecules in human pre-implantation 30 embryos. We demonstrate complement attack against early embryos, and show presence of 31 embryonic defence mechanisms. Furthermore, we reveal early embryonic production of 32 complement activators, suggesting non-canonical roles in cell signalling and development. Our 33 findings thus reveal a fundamental role for complement at the earliest stages of human 34 embryogenesis. Our data opens up for future studies into the role of complement, both in 35 relation to infertility and pregnancy complications, as well as basic cellular processes during 36 early human development. 37 38 3
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.