Antigen-Specific Antibody Glycosylation Is Regulated via Vaccination.

Antibody effector functions, such as antibody-dependent cellular cytotoxicity, complement deposition, and antibody-dependent phagocytosis, play a critical role in immunity against multiple pathogens, particularly in the absence of neutralizing activity. Two modifications to the IgG constant domain (Fc domain) regulate antibody functionality: changes in antibody subclass and changes in a single N-linked glycan located in the CH2 domain of the IgG Fc. Together, these modifications provide a specific set of instructions to the innate immune system to direct the elimination of antibody-bound antigens. While it is clear that subclass selection is actively regulated during the course of natural infection, it is unclear whether antibody glycosylation can be tuned, in a signal-specific or pathogen-specific manner. Here, we show that antibody glycosylation is determined in an antigen- and pathogen-specific manner during HIV infection. Moreover, while dramatic differences exist in bulk IgG glycosylation among individuals in distinct geographical locations, immunization is able to overcome these differences and elicit antigen-specific antibodies with similar antibody glycosylation patterns. Additionally, distinct vaccine regimens induced different antigen-specific IgG glycosylation profiles, suggesting that antibody glycosylation is not only programmable but can be manipulated via the delivery of distinct inflammatory signals during B cell priming. These data strongly suggest that the immune system naturally drives antibody glycosylation in an antigen-specific manner and highlights a promising means by which next-generation therapeutics and vaccines can harness the antiviral activity of the innate immune system via directed alterations in antibody glycosylation in vivo. .

Correction: Antigen-Specific Antibody Glycosylation Is Regulated via Vaccination.

[This corrects the article DOI: 10.1371/journal.ppat.1005456.].

Atmospheric record in the Hadean Eon from multiple sulfur isotope measurements in Nuvvuagittuq Greenstone Belt (Nunavik, Quebec).

Mass-independent fractionation of sulfur isotopes (S-MIF) results from photochemical reactions involving short-wavelength UV light. The presence of these anomalies in Archean sediments [(4-2.5 billion years ago, (Ga)] implies that the early atmosphere was free of the appropriate UV absorbers, of which ozone is the most important in the modern atmosphere. Consequently, S-MIF is considered some of the strongest evidence for the lack of free atmospheric oxygen before 2.4 Ga. Although temporal variations in the S-MIF record are thought to depend on changes in the abundances of gas and aerosol species, our limited understanding of photochemical mechanisms complicates interpretation of the S-MIF record in terms of atmospheric composition. Multiple sulfur isotope compositions (δ(33)S, δ(34)S, and δ(36)S) of the >3.8 billion-year-old Nuvvuagittuq Greenstone Belt (Ungava peninsula) have been investigated to track the early origins of S-MIF. Anomalous S-isotope compositions (Δ(33)S up to +2.2‰) confirm a sedimentary origin of sulfide-bearing banded iron and silica-rich formations. Sharp isotopic transitions across sedimentary/igneous lithological boundaries indicate that primary surficial S-isotope compositions have been preserved despite a complicated metamorphic history. Furthermore, Nuvvuagittuq metasediments recorded coupled variations in (33)S/(32)S, (34)S/(32)S, and (36)S/(32)S that are statistically indistinguishable from those identified several times later in the Archean. The recurrence of the same S-isotope pattern at both ends of the Archean Eon is unexpected, given the complex atmospheric, geological, and biological pathways involved in producing and preserving this fractionation. It implies that, within 0.8 billion years of Earth's formation, a common mechanism for S-MIF production was established in the atmosphere.

Evidence for the survival of the oldest terrestrial mantle reservoir.

Helium is a powerful tracer of primitive material in Earth's mantle. Extremely high (3)He/(4)He ratios in some ocean-island basalts suggest the presence of relatively undegassed and undifferentiated material preserved in Earth's mantle. However, terrestrial lavas with high (3)He/(4)He ratios have never been observed to host the primitive lead-isotopic compositions that are required for an early (roughly 4.5 Gyr ago) formation age. Here we show that Cenozoic-era Baffin Island and West Greenland lavas, previously found to host the highest terrestrial-mantle (3)He/(4)He ratios, exhibit primitive lead-isotope ratios that are consistent with an ancient mantle source age of 4.55-4.45 Gyr. The Baffin Island and West Greenland lavas also exhibit (143)Nd/(144)Nd ratios similar to values recently proposed for an early-formed (roughly 4.5 Gyr ago) terrestrial mantle reservoir. The combined helium-, lead- and Nd-isotopic compositions in Baffin Island and West Greenland lavas therefore suggest that their source is the most ancient accessible reservoir in the Earth's mantle, and it may be parental to all mantle reservoirs that give rise to modern volcanism.

Preservation of Earth-forming events in the tungsten isotopic composition of modern flood basalts.

How much of Earth's compositional variation dates to processes that occurred during planet formation remains an unanswered question. High-precision tungsten isotopic data from rocks from two large igneous provinces, the North Atlantic Igneous Province and the Ontong Java Plateau, reveal preservation to the Phanerozoic of tungsten isotopic heterogeneities in the mantle. These heterogeneities, caused by the decay of hafnium-182 in mantle domains with high hafnium/tungsten ratios, were created during the first ~50 million years of solar system history, indicating that portions of the mantle that formed during Earth's primary accretionary period have survived to the present.

Neodymium-142 evidence for Hadean mafic crust.

Neodymium-142 data for rocks from the Nuvvuagittuq greenstone belt in northern Quebec, Canada, show that some rock types have lower 142Nd/144Nd ratios than the terrestrial standard (epsilon142Nd = -0.07 to -0.15). Within a mafic amphibolite unit, 142Nd/144Nd ratios correlate positively with Sm/Nd ratios and produce a 146Sm-142Nd isochron with an age of 4280(-81)(+53) million years. These rocks thus sample incompatible-element-enriched material formed shortly after Earth formation and may represent the oldest preserved crustal section on Earth.