Early appearance of functional plasma cells (CD138+CD98+) in non-immunized neonate mice.

Plasma cells (PCs) are terminally differentiated antibody-secreting cells, derived from activated B-lymphocytes in response to either T-independent or T-dependent antigens. The plasma cell population is scarce in circulation in non-immunized individuals. It is established that neonates are incapable of mounting an efficient immune response due to the immaturity of the immune system. However, this disadvantage is well overcome through the antibodies neonates receive from breastmilk. This implies that neonates will be only protected against antigens the mother had previously encountered. Thus, the child might be potentially susceptible to new antigens. This issue prompted us to seek for the presence of PCs in non-immunized neonate mice. We found a PC population identified as CD138+/CD98+ cells since day one after birth. These PCs were positive for Ki67 and expressed Blimp-1, B220, and CD19, which suggests the populations are plasmablasts and PCs with heterogeneous phenotype. These PCs were also determined to secrete antibodies, although mainly isotype IgM. Altogether, the results indicated that neonate PCs can produce antibodies against antigens they encounter in the first weeks of life, most likely coming from food, colonizing microbiota, or the environment.

Chronic intake of moderate fat-enriched diet induces fatty liver and low-grade inflammation without obesity in rabbits.

Non-Alcoholic Fatty Liver Disease (NAFLD) is the cause of chronic liver disease. Even though NAFLD is strongly associated with obesity and metabolic syndrome, there is a proportion of patients who develop this condition in the absence of obesity and the underlying mechanisms are poorly understood. We investigated early events in the pathogenesis of non-obese NAFLD, analyzing the impact of the chronic intake of a moderate fat-enriched diet on hepatic lipid accumulation and their relationship with inflammation. Rabbits fed with a moderate Fatty-Acid- Enriched Diet 3% palmitic acid (FAED), were evaluated for body weight, biochemical parameters, and liver function. Liver samples were analyzed by histology and RT-qPCR to measure lipid accumulation, the expression of inflammation-related genes IL-1ß, IL-6, IL-10, IL-13, IL-18, COX-2, TNF-α, and TLR-4. Chronic consumption by 6-months of FAED did not generate metabolic changes, but it induced fatty liver. We also observed the development of low-grade inflammation characterized by the up regulation of TNF-α, IL-13 and IL-18. The consumption by 12-months of FAED caused the overexpression of IL-6, IL-10, IL-13, COX-2, and TLR-4. We show that hepatic steatosis is an early consequence of fat-enriched diets, and that it is accompanied by an immune response that exerts protective effects that prevent the development of metabolic disorders, such as overweight/obesity and metabolic syndrome. However, the excessive intake of fatty acids renders these mechanisms less efficient for delaying the start of metabolic alterations. Rabbits fed with FAED can be used as a model of NAFLD in non-obese and obese groups, especially at early stages of the disease.