Summary Systemic Lupus Erythematosus (SLE) is characterized by B-cells lacking IgD and CD27 (double negative; DN). We show that DN cell expansions reflected a subset of CXCR5−CD11c+ cells (DN2) representing pre-plasma cells (PC). DN2 cells predominated in African-American patients with active disease and nephritis, anti-Smith and anti-RNA autoantibodies. They expressed a T-bet transcriptional network; increased toll-like receptor-7 (TLR7); lacked the negative TLR regulator TRAF5; and were hyper-responsive to TLR7. DN2 cells shared with activated naïve cells (aNAV), phenotypic and functional features, and similar transcriptomes. Their PC differentiation and autoantibody production was driven by TLR7 in an interleukin-21 (IL-21)-mediated fashion. An in vivo developmental link between aNAV, DN2 cells and PC was demonstrated by clonal sharing. This study defines a distinct differentiation fate of autoreactive naïve B cells into PC precursors with hyper-responsiveness to innate stimuli, as well as establishes prominence of extra-follicular B-cell activation in SLE, and identifies therapeutic targets.

Single-atom catalysts often exhibit unexpected catalytic activity for many important chemical reactions because of their unique electronic and geometric structures with respect to their bulk counterparts. Herein we adopt metal-organic frameworks (MOFs) to assist the preparation of a catalyst containing single Ni sites for efficient electroreduction of CO. The synthesis is based on ionic exchange between Zn nodes and adsorbed Ni ions within the cavities of the MOF. This single-atom catalyst exhibited an excellent turnover frequency for electroreduction of CO (5273 h), with a Faradaic efficiency for CO production of over 71.9% and a current density of 10.48 mA cm at an overpotential of 0.89 V. Our findings present some guidelines for the rational design and accurate modulation of nanostructured catalysts at the atomic scale.

The design of active, selective, and stable CO reduction electrocatalysts is still challenging. A series of atomically dispersed Co catalysts with different nitrogen coordination numbers were prepared and their CO electroreduction catalytic performance was explored. The best catalyst, atomically dispersed Co with two-coordinate nitrogen atoms, achieves both high selectivity and superior activity with 94 % CO formation Faradaic efficiency and a current density of 18.1 mA cm at an overpotential of 520 mV. The CO formation turnover frequency reaches a record value of 18 200 h , surpassing most reported metal-based catalysts under comparable conditions. Our experimental and theoretical results demonstrate that lower a coordination number facilitates activation of CO to the CO intermediate and hence enhances CO electroreduction activity.