The miR-17∼92 miRNAs promote plasma cell differentiation by suppressing SOCS3-mediated NIK degradation.

The miR-17∼92 family microRNAs (miRNAs) play a key role in germinal center (GC) reaction through promoting T follicular helper (TFH) cell differentiation. It remains unclear whether they also have intrinsic functions in B cell differentiation and function. Here we show that mice with B cell-specific deletion of the miR-17∼92 family exhibit impaired GC reaction, plasma cell differentiation, and antibody production in response to protein antigen immunization and chronic viral infection. Employing CRISPR-mediated functional screening, we identify Socs3 as a key functional target of miR-17∼92 in regulating plasma cell differentiation. Mechanistically, SOCS3, whose expression is elevated in miR-17∼92 family-deficient B cells, interacts with NIK and promotes its ubiquitination and degradation, thereby impairing NF-κB signaling and plasma cell differentiation. This moderate increase in SOCS3 expression has little effect on IL-21-STAT3 signaling. Our study demonstrates differential sensitivity of two key signaling pathways to alterations in the protein level of an miRNA target gene.

Dhx33 promotes B-cell growth and proliferation by controlling activation-induced rRNA upregulation.

Upon recognition of foreign antigens, naïve B cells undergo rapid activation, growth, and proliferation. How B-cell growth and proliferation are coupled with activation remains poorly understood. Combining CRISPR/Cas9-mediated functional analysis and mouse genetics approaches, we found that Dhx33, an activation-induced RNA helicase, plays a critical role in coupling B-cell activation with growth and proliferation. Mutant mice with B-cell-specific deletion of Dhx33 exhibited impaired B-cell development, germinal center reactions, plasma cell differentiation, and antibody production. Dhx33-deficient B cells appeared normal in the steady state and early stage of activation but were retarded in growth and proliferation. Mechanistically, Dhx33 played an indispensable role in activation-induced upregulation of ribosomal DNA (rDNA) transcription. In the absence of Dhx33, activated B cells were compromised in their ability to ramp up 47S ribosomal RNA (rRNA) production and ribosome biogenesis, resulting in nucleolar stress, p53 accumulation, and cellular death. Our findings demonstrate an essential role for Dhx33 in coupling B-cell activation with growth and proliferation and suggest that Dhx33 inhibition is a potential therapy for lymphoma and antibody-mediated autoimmune diseases.

Phycocomes zhengii gen. nov., sp. nov., a marine bacterium of the family Rhodobacteraceae isolated from the phycosphere of Chlorella vulgaris.

A Gram-stain-negative, motile with flagellum, ovoid- or rod-shaped, aerobic bacterium, was isolated from the phycosphere of the microalga Chlorellavulgaris and designated as strain LMIT002T. The bacterium formed white, circular and smooth colonies on marine agar 2216 after 48 h incubation at 25 °C. On the basis of 16S rRNA gene sequence analysis, strain LMIT002T was found to be affiliated with the family Rhodobacteraceae of the order Rhodobacterales, and formed a distinct group. The 16S rRNA gene sequence similarities between strain LMIT002T and type strains in the family including Poseidonocella pacifica DSM 29316T, Roseobacter litoralis and Rhodovulum sulfidophilum were 95.1, 95.0 and 95.0 %, respectively. Strain LMIT002Tgrew optimally at 25 °C, pH 6.0 and in the presence of 2.0 % (w/v) NaCl. The genomic DNA G+C content was 67.0 mol% (the thermal denaturation method) or 66.9 % (genome sequencing). The sole respiratory quinone was ubiquinone-8, while the major fatty acids were summed feature 8 (C18 : 1 ω7с/C18 : 1 ω6с). The draft genome of strain LMIT002T was sequenced and annotated, with the results showing that it had a total size of 4 607 780 bp and comprised 4557 genes. Functional genes encoding the production of vitamin B12, indole-3-acetic acid and transform dimethylsulphoniopropionate were detected. Given its distinct genomic, morphological and physiological differences from previously described type strains, strain LMIT002T is proposed as a representative of a novel genus of the family Rhodobacteraceae, with the name Phycocomes zhengii gen. nov., sp. nov. The type strain is LMIT002T (=KCTC 62390T=CICC 24357T).