Fibroblastic reticular cell lineage convergence in Peyer’s patches governs intestinal immunity

Fibroblastic reticular cells (FRCs) determine the organization of lymphoid organs and control immune cell interactions. While the cellular and molecular mechanisms underlying FRC differentiation in lymph nodes and the splenic white pulp have been elaborated to some extent, in Peyer’s patches (PPs) they remain elusive. Using a combination of single-cell transcriptomics and cell fate mapping in advanced mouse models, we found that PP formation in the mouse embryo is initiated by an expansion of perivascular FRC precursors, followed by FRC differentiation from subepithelial progenitors. Single-cell transcriptomics and cell fate mapping confirmed the convergence of perivascular and subepithelial FRC lineages. Furthermore, lineage-specific loss- and gain-of-function approaches revealed that the two FRC lineages synergistically direct PP organization, maintain intestinal microbiome homeostasis and control anticoronavirus immune responses in the gut. Collectively, this study reveals a distinct mosaic patterning program that generates key stromal cell infrastructures for the control of intestinal immunity. © 2021, The Author(s), under exclusive licence to Springer Nature America, Inc. part of Springer Nature

Lymphatic Endothelial Cells Control Initiation of Lymph Node Organogenesis

Lymph nodes (LNs) are strategically situated throughout the body at junctures of the blood vascular and lymphatic systems to direct immune responses against antigens draining from peripheral tissues. The current paradigm describes LN development as a programmed process that is governed through the interaction between mesenchymal lymphoid tissue organizer (LTo) cells and hematopoietic lymphoid tissue inducer (LTi) cells. Using cell-type-specific ablation of key molecules involved in lymphoid organogenesis, we found that initiation of LN development is dependent on LTi-cell-mediated activation of lymphatic endothelial cells (LECs) and that engagement of mesenchymal stromal cells is a succeeding event. LEC activation was mediated mainly by signaling through receptor activator of NF-kappa B (RANK) and the non-canonical NF-kappa B pathway and was steered by sphingosine-1-phosphate-receptor-dependent retention of LTi cells in the LN anlage. Finally, the finding that pharmacologically enforced interaction between LTi cells and LECs promotes ectopic LN formation underscores the central LTo function of LECs

DESMEX: A novel system development for semi-airborne electromagnetic exploration

There is a clear demand to increase detection depths in the context of raw material exploration programs. Semi-airborne electromagnetic (semi-AEM) methods can address these demands by combining the advantages of powerful transmitters deployed on the ground with efficient helicopter-borne mapping of the magnetic field response in the air.The penetration depth can exceed those of classical airborne EM systems,since low frequencies and large transmitter-receiver offsets can be realized in practice. A novel system has been developed that combines high-moment horizontal electric bipole transmitters on the ground with low-noise three-axis induction coilmagnetometers, a three-axis fluxgate magnetometer and a laser gyroinertial measurement unit integrated within a helicopter-towed airborne platform. The attitude data are used to correct the time series for motional noise and subsequently to rotate into an Earth-fixed reference frame. In a second processing step, and as opposed to existing semi-airborne systems, we transform the data into the frequency domain and estimate the complex-valued transfer functions between the received magnetic field components and the synchronously recorded injection current by regression analysis. This approach is similar to the procedure employed in controlled-source EM. For typical source bipole moments of 20-40 kAm and for rectangular current waveforms with a fundamental frequency of about 10 Hz, we can estimate reliable three-component transfer functions in the frequency range from 10-5000 Hz over a measurement area of 4 x 5 km2 for a single source installation. The system has the potential to be used for focused exploration of deep targets

B cell zone reticular cell microenvironments shape CXCL13 gradient formation

Through the formation of concentration gradients, morphogens drive graded responses to extracellular signals, thereby fine-tuning cell behaviors in complex tissues. Here we show that the chemokine CXCL13 forms both soluble and immobilized gradients. Specifically, CXCL13+ follicular reticular cells form a small-world network of guidance structures, with computer simulations and optimization analysis predicting that immobilized gradients created by this network promote B cell trafficking. Consistent with this prediction, imaging analysis show that CXCL13 binds to extracellular matrix components in situ, constraining its diffusion. CXCL13 solubilization requires the protease cathepsin B that cleaves CXCL13 into a stable product. Mice lacking cathepsin B display aberrant follicular architecture, a phenotype associated with effective B cell homing to but not within lymph nodes. Our data thus suggest that reticular cells of the B cell zone generate microenvironments that shape both immobilized and soluble CXCL13 gradients

The nucleotide sequence of Saccharomyces cerevisiae chromosome IV

Jacq C, Alt-Mörbe J, Andre B, et al. The nucleotide sequence of Saccharomyces cerevisiae chromosome IV. Nature. 1997;387(6632 Suppl):75-78