Classical monocyte ontogeny dictates their functions and fates as tissue macrophages.

Classical monocytes (CMs) are ephemeral myeloid immune cells that circulate in the blood. Emerging evidence suggests that CMs can have distinct ontogeny and originate from either granulocyte-monocyte- or monocyte-dendritic-cell progenitors (GMPs or MDPs). Here, we report surface markers that allowed segregation of murine GMP- and MDP-derived CMs, i.e., GMP-Mo and MDP-Mo, as well as their functional characterization, including fate definition following adoptive cell transfer. GMP-Mo and MDP-Mo yielded an equal increase in homeostatic CM progeny, such as blood-resident non-classical monocytes and gut macrophages; however, these cells differentially seeded various other selected tissues, including the dura mater and lung. Specifically, GMP-Mo and MDP-Mo differentiated into distinct interstitial lung macrophages, linking CM dichotomy to previously reported pulmonary macrophage heterogeneity. Collectively, we provide evidence for the existence of two functionally distinct CM subsets in the mouse that differentially contribute to peripheral tissue macrophage populations in homeostasis and following challenge.

T cell help induces Myc transcriptional bursts in germinal center B cells during positive selection.

Antibody affinity maturation occurs in secondary lymphoid organs within germinal centers (GCs). At these sites, B cells mutate their antibody-encoding genes in the dark zone, followed by preferential selection of the high-affinity variants in the light zone by T cells. The strength of the T cell-derived selection signals is proportional to the B cell receptor affinity and to the magnitude of subsequent Myc expression. However, because the lifetime of Myc mRNA and its corresponding protein is very short, it remains unclear how T cells induce sustained Myc levels in positively selected B cells. Here, by direct visualization of mRNA and active transcription sites in situ, we found that an increase in transcriptional bursts promotes Myc expression during B cell positive selection in GCs. Elevated T cell help signals predominantly enhance the percentage of cells expressing Myc in GCs as opposed to augmenting the quantity of Myc transcripts per individual cell. Visualization of transcription start sites in situ revealed that T cell help promotes an increase in the frequency of transcriptional bursts at the Myc locus in GC B cells located primarily in the LZ apical rim. Thus, the rise in Myc, which governs positive selection of B cells in GCs, reflects an integration of transcriptional activity over time rather than an accumulation of transcripts at a specific time point.

Oscillations and slow patterning in the antennal lobe.

Odor presentation generates both fast oscillations and slow patterning in the spiking activity of the projection neurons (PNs) in the antennal lobe (AL) of locusts, moths and bees. Experimental results indicate that the oscillations are the result of the interaction between the PNs and the inhibitory local neurons (LNs) in the AL; e.g., blocking inhibition by application of GABA-receptor antagonists abolishes these oscillations. The slow patterning, on the other hand, was shown to be somewhat resistant to such blockage. In a H-H model, we reproduce both the oscillations and the slow patterning. As previously suggested, the oscillations are the result of the interaction between the PNs and LNs. We suggest that calcium and calcium-dependent potassium channels (found in PNs of bees and moths) are sufficient to account for the slow patterning resistant to the application of GABA-receptor antagonists. The intrinsic bursting property of the PNs, resulting from these additional modeled currents, give rise to another network feature that was seen experimentally in locusts: A relatively small increase in the number of additional generated PN action potentials when LN input is blocked. Consequently, the major effect of network inhibition is to redistribute the action potentials of the PNs from bursting to one action potential per cycle of the oscillations.

Mechanism and circuitry for clustering and fine discrimination of odors in insects.

Odor recognition encompasses both clustering and fine discrimination. Clustering joins together sets of odors, and fine discrimination distinguishes between odors belonging to the same cluster. We hypothesize that these two aspects of odor recognition are encoded in parallel by two brain areas of the insect olfactory system. Population activity of neurons in the lateral horn encodes the odor cluster, and population activity of neurons in the mushroom body encodes the fine identity of the odor. Our mechanism is based on the hypothesis that the underlying network of the insect olfactory system consists of a repetitive, hard-wired substructure whose anatomy we describe. We show that these suggested mechanisms and circuitry explain not only the observed numbers and connections of neurons in the system, but also the observed activity of these neurons, and why oscillations are critical for fine discrimination but not for clustering of odors.