Biology subjects

Robinson, A. M.

Publications and source records attributed to Robinson, A. M..

3 recordsLinked to original sources

bioRxiv2022

Lead (Pb) impairs thyroid hormone mediated changes in brain development and body length in Xenopus laevis tadpoles

Lead (Pb) poisoning during early development is associated with behavioral and cognitive deficits, but the specific mechanisms by which Pb impairs brain development are not fully understood. One potential mechanism is that Pb poisoning may impair thyroid hormone (TH)- mediated changes in brain development To address this issue, we performed experiments to assess the effects of Pb poisoning on (TH) -dependent changes in cellular and molecular mechanisms in the developing Xenopus laevis tadpole brain. We treated stage 48 tadpoles to combinations of 1000 ppb Pb bath for seven days and added one of three different concentrations of thyroxine (T4) for the final two days of treatment. We found that lead exposure decreased body length, including in T4-treated tadpoles. We also performed immuno-staining for proliferative marker pH3 and found that Pb disrupts T4-induced increases in neuronal proliferation. Finally, we used syGlass VR data visualization software to measure volume of the forebrain, midbrain, and hindbrain in 3D and found that Pb exposure impaired T4-mediated changes in brain volume. Last, we found that Pb poisoning reduced the T4-mediated increase in proliferating cell nuclear antigen (PCNA), a TH-sensitive gene. These results illustrate that Pb poisoning impairs some TH-dependent changes in the developing brain.

pharmacology and toxicology↗

bioRxiv2021

Evolution of antigen-specific follicular helper T cell transcriptional programs across effector function and through to memory

Understanding how follicular helper T cells (TFH) regulate the specialization, maturation, and differentiation of adaptive B cell immunity is crucial for developing durable high-affinity immune protection. Using indexed-single cell molecular strategies, we reveal a skewed intra-clonal assortment of higher affinity TCR and the distinct molecular programming of the localized TFH compartment compared to emigrant conventional effector TH (ETH) cells. We find a temporal shift in BCR class switch which permits identification of inflammatory and anti-inflammatory modules of transcriptional programming that subspecialize TFH function before and during the germinal center (GC) reaction. Late collapse of this local primary GC reaction reveals a persistent post-GC TFH population which discloses a putative memory TFH program. These studies define specialized antigen-specific TFH transcriptional programs that progressively direct class-specific evolution of high-affinity B cell immunity and uncover the transcriptional program of a memory TFH population as the regulators of antigen recall. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=149 SRC="FIGDIR/small/460841v1_ufig1.gif" ALT="Figure 1"> View larger version (48K): org.highwire.dtl.DTLVardef@17413c2org.highwire.dtl.DTLVardef@1bd505borg.highwire.dtl.DTLVardef@1e6bc99org.highwire.dtl.DTLVardef@167e6e9_HPS_FORMAT_FIGEXP M_FIG C_FIG SummaryDistinct inflammatory and anti-inflammatory antigen-specific TFH transcriptional programs regulate class-specific B cell maturation. Highlights- Skewed intra-clonal assortment of high affinity TCR into the TFH compartment - Significant temporal delay in anti-inflammatory IgG1 production - Inflammatory and anti-inflammatory transcriptional modules subspecialize TFH - Late GC collapse reveals a persisting post-GC putative memory TFH compartment

immunology↗

bioRxiv2021

Programming isotype specific plasma cell differentiation

Antibodies are produced across multiple isotypes with distinct properties that coordinate initial antigen clearance and confer long-term antigen-specific immune protection. Here, we interrogate the molecular programs of isotype-specific murine plasma cells (PC) following helper T cell dependent immunization and within established steady-state immunity. Using integrated single cell strategies, we reveal conserved and divergent components of the rapid effector phase of antigen-specific IgM+ versus inflammation modulating programs dictated by IgG2a/b+ PC differentiation. During antibody affinity maturation, the germinal center (GC) cycle imparts separable programs for post-GC inhibitory IgG1+ and inflammatory IgG2a/b+ PC to direct long-term cellular function. In the steady-state, two subsets of IgM+ and separate IgG2b+ PC programs clearly segregate from splenic IgA+ PC programs that emphasize mucosal barrier protection. These diverse isotype-specific molecular pathways of PC differentiation control complementary modules of antigen clearance and immune protection that could be selectively targeted for immunotherapeutic applications and vaccine design.

immunology↗