Asymmetrical forward and reverse developmental trajectories determine molecular programs of B cell antigen receptor editing

Science Immunology, 2022

We demonstrated that autoreactive B cells transit asymmetric forward and reverse developmental trajectories. This imparted a unique epigenetic landscape on small pre-B cells, which opened chromatin to transcription factors essential for Igλ recombination. The consequences of this asymmetric developmental path were both amplified and complemented by CXCR4 signaling. These findings reveal how intrinsic molecular programs integrate with extrinsic signals to drive receptor editing.

Specific in situ inflammatory states associate with progression to renal failure in lupus nephritis

Journal of Clinical Investigation, 2022

We interrogated renal biopsies from lupus nephritis longitudinal and cross-sectional cohorts. High B cell densities were associated with protection from end-stage renal disease (ESRD). In contrast, high densities of CD8+, γδ, and other CD4-CD8- T cells were associated with both acute renal failure and progression to ESRD. B cells were often organized into large periglomerular neighborhoods with Tfh cells, while CD4- T cells formed small neighborhoods in the tubulointerstitium, with frequency that predicted progression to ESRD. These data reveal that specific in situ inflammatory states are associated with refractory and progressive renal disease.

Novel specialized cell state and spatial compartments within the germinal center

Nature Immunology, 2020

We demonstrate that, during germinal center reactions and following selection in the Light Zone (LZ), B cells migrate to specialized sites within the canonical Dark Zone (DZ) that contained tingible body macrophages and were sites of ongoing cell division. Proliferating DZ (DZp) cells then transited into the larger DZ to become differentiating DZ (DZd) cells before re-entering the LZ. We reveal distinct molecular programs in each germinal center population and provide a new three-cell population model of the germinal center.