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Ig diversification occurs in peripheral lymphoid organs after establishment of central tolerance during B cell development. In germinal centers (GCs), somatic hypermutation of Ig genes occurs in dark zones, followed by selection of mutated clones in light zones (LZs). This generates high-affinity Ig receptors to pathogens but can also produce autoreactive Ig receptors, which are removed by selection mechanisms that are incompletely understood. The ubiquitin ligase Itch prevents the emergence of autoimmune disease and autoantibodies in humans and mice, and patients lacking Itch develop potentially fatal autoimmune diseases; yet, how Itch regulates GC B cells is not well understood. By studying Itch-deficient mice, we have recently shown that Itch directly limits the magnitude of GC responses. Proteomic profiling of GC B cells uncovered that Itch-deficient cells exhibit high mTORC1 and Myc activity, hallmarks of positive selection. Bone marrow chimera and adoptive transfer experiments revealed that B cell Itch restricts noncycling LZ cells. These results support, to our knowledge, a novel role for Itch in skewing selection of GC B cells to restrict LZ accumulation and shape GC-derived humoral immunity. Determining how B cells integrate cues within GCs to navigate through LZs and dark zones will aid in understanding how autoreactive clones emerge from GCs in people with autoimmune disease.

The thermal Sunyaev-Zel'dovich (tSZ) effect is a powerful tool with the potential for constraining directly the properties of the hot gas that dominates dark matter halos because it measures pressure and thus thermal energy density. Studying this hot component of the circumgalactic medium (CGM) is important because it is strongly impacted by star-formation and active galactic nuclei (AGN) activity in galaxies, participating in the feedback loop that regulates star and black hole mass growth in galaxies. We study the tSZ effect across a wide halo mass range using three cosmological hydrodynamical simulations: Illustris-TNG, EAGLE, and FIRE-2. Specifically, we present the scaling relation between tSZ signal and halo mass and radial profiles of gas density, temperature, and pressure for all three simulations. The analysis includes comparisons to Planck tSZ observations and to the thermal pressure profile inferred from the Atacama Cosmology Telescope (ACT) measurements. We compare these tSZ data to the simulations to interpret the measurements in terms of feedback and accretion processes in the CGM. We also identify as-yet unobserved potential signatures of these processes that may be visible in future measurements, which will have the capability of measuring tSZ signals to even lower masses. We also perform internal comparisons between runs with different physical assumptions. We conclude: (1) there is strong evidence for the impact of feedback at $R_{500}$ but that this impact decreases by $5R_{500}$, and (2) the thermodynamic profiles of the CGM are highly dependent on the implemented model, such as cosmic-ray or AGN feedback prescriptions., 21 pages, 10 figures, submitted to ApJ, comments welcome