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Affinity-matured plasma cells (PCs) of varying lifespans are generated through a germinal center (GC) response. The developmental dynamics and genomic programs of antigen-specific PC precursors remain to be elucidated. Here, using a model antigen in mice, we demonstrate biphasic generation of PC precursors, with those generating long-lived bone marrow PCs preferentially produced in the late phase of GC response. Clonal tracing using single-cell RNA sequencing and B cell antigen receptor sequencing in spleen and bone marrow compartments, coupled with adoptive transfer experiments, reveals a new PC transition state that gives rise to functionally competent PC precursors. The latter undergo clonal expansion, dependent on inducible expression of TIGIT. We propose a model for the proliferation and programming of precursors of long-lived PCs, based on extended antigen encounters in the GC.

Antigen-activated B cells diversify variable regions of B cell antigen receptors by somatic hypermutation in germinal centers (GCs). The positive selection of GC B cells that acquire high-affinity mutations enables antibody affinity maturation. In spite of considerable progress, the genomic states underlying this process remain to be elucidated. Single-cell RNA sequencing and topic modeling revealed increased expression of the oxidative phosphorylation (OXPHOS) module in GC B cells undergoing mitoses. Coupled analysis of somatic hypermutation in immunoglobulin heavy chain (Igh) variable gene regions showed that GC B cells acquiring higher-affinity mutations had further elevated expression of OXPHOS genes. Deletion of mitochondrial Cox10in GC B cells resulted in reduced cell division and impaired positive selection. Correspondingly, augmentation of OXPHOS activity with oltipraz promoted affinity maturation. We propose that elevated OXPHOS activity promotes B cell clonal expansion and also positive selection by tuning cell division times.

In order to decrease the number of design variables and improve the efficiency of composite structure optimal design, a single-level composite structure optimization method based on a tapered model is presented. Compared with the conventional multi-level composite structure optimization method, this single-level method has many advantages. First, by using a distance variable and a ply group variable, the number of design variables is decreased evidently and independent with the density of sub-regions, which makes the single-level method very suitable for large-scale composite structures. Second, it is very convenient to optimize laminate thickness and stacking sequence in the same level, which probably improves the quality of optimal result. Third, ply continuity can be guaranteed between sub-regions in the single-level method, which could reduce stress concentration and manufacturing difficulty. An example of a composite wing is used to demonstrate the advantages and competence of the single-level method proposed.