Follicular T-helper (T FH ) cells cooperate with GL7 + CD95 + germinal center (GC) B cells to induce antibody maturation. Herein, we identify the transcription factor IRF4 as a T-cell intrinsic precondition for T FH cell differentiation and GC formation. After immunization with protein or infection with the protozoon Leishmania major , draining lymph nodes (LNs) of IFN-regulatory factor-4 ( Irf4 −/− ) mice lacked GCs and GC B cells despite developing normal initial hyperplasia. GCs were also absent in Peyer’s patches of naive Irf4 −/− mice. Accordingly, CD4 + T cells within the LNs and Peyer’s patches failed to express the T FH key transcription factor B-cell lymphoma-6 and other T FH -related molecules. During chronic leishmaniasis, the draining Irf4 −/− LNs disappeared because of massive cell death. Adoptive transfer of WT CD4 + T cells or few L. major primed WT T FH cells reconstituted GC formation, GC B-cell differentiation, and LN cell survival. In support of a T-cell intrinsic IRF4 activity, Irf4 −/− T FH cell differentiation was not rescued by close neighborhood to transferred WT T FH cells. Together with its known B lineage-specific roles during plasma cell maturation and class switch, our study places IRF4 in the center of antibody production toward T-cell–dependent antigens.

Known predictive factors for VMT resolution after ocriplasmin IVI were confirmed in our study. We were able to combine them into a formula, ultimately allowing the calculation of an individual probability of treatment success with ocriplasmin in patients with VMT syndrome without FTHM.

The genus leishmania comprises different protozoan parasites which are causative agents of muco-cutaneous and systemic, potentially lethal diseases. After infection with the species Leishmania major, resistant mice expand Th1 cells which stimulate macrophages for Leishmania destruction. In contrast, susceptible mice generate Th2 cells which deactivate macrophages, leading to systemic spread of the pathogens. Th-cell differentiation is determined within the first days, and Th2 cell differentiation requires IL-4, whereby the initial IL-4 source is often unknown. Mast cells are potential sources of IL-4, and hence their role in murine leishmaniasis has previously been studied in mast cell-deficient Kit mutant mice, although these mice display immunological phenotypes beyond mast cell deficiency. We therefore readdressed this question by infecting Kitindependent mast cell-deficient mice that are Th1 (C57BL/6 Cpa Cre ) or Th2 (BALB/c Cpa Cre ) prone with L. major. Using different parasite doses and intra-or subcutaneous infection routes, the results demonstrate no role of mast cells on lesion size development, parasite load, immune cell phenotypes expanding in draining lymph nodes, and cytokine production during murine cutaneous leishmaniasis. Thus, other cell types such as ILCs or T cells have to be considered as primary source of Th2-driving IL-4. Additional supporting information may be found in the online version of this article at the publisher's web-site Keywords

The angle between the posterior vitreous cortex and the internal limiting membrane 500 μm apart from the fovea centralis correlates with VMT resolution and may be a clinically useful marker for selection of patients to be treated with ocriplasmin. This observation needs to be proven in a prospective confirmatory investigation.

The processes leading from disturbed B-cell development to adult B-cell progenitor acute lymphoblastic leukemia (BCP-ALL) remain poorly understood. Here, we describe Irf4−/− mice as prone to developing BCP-ALL with age. Irf4−/− preB-I cells exhibited impaired differentiation but enhanced proliferation in response to IL-7, along with reduced retention in the IL-7 providing bone marrow niche due to decreased CXCL12 responsiveness. Thus selected, preB-I cells acquired Jak3 mutations, probably following irregular AID activity, resulting in malignant transformation. We demonstrate heightened IL-7 sensitivity due to Jak3 mutants, devise a model to explain it, and describe structural and functional similarities to Jak2 mutations often occurring in human Ph-like ALL. Finally, targeting JAK signaling with Ruxolitinib in vivo prolonged survival of mice bearing established Irf4−/− leukemia. Intriguingly, organ infiltration including leukemic meningeosis was selectively reduced without affecting blood blast counts. In this work, we present spontaneous leukemogenesis following IRF4 deficiency with potential implications for high-risk BCP-ALL in adult humans.

PURPOSE: To assess patient satisfaction and quality of life after refractive lens exchange with a trifocal intraocular lens (IOL). METHODS: Consecutive patients who underwent refractive lens exchange with the AT LISA tri or AT LISA tri toric IOL (Carl Zeiss Meditec AG) at one of five surgical centers were surveyed for their quality of life and satisfaction after surgery using a standardized questionnaire. Patient responses were compared to patient characteristics such as age, sex, axial lengths, and preoperative refraction. RESULTS: A total of 102 patients with 204 treated eyes were included in the analysis. The mean age was 54.6 ± 5.2 years. A total of 172 eyes were hypermetropic, 3 were emmetropic, and 25 were myopic, with a mean preoperative refractive error of 0.93 ± 2.17 diopters. Reported postoperative satisfaction was as follows: 81.4% stated that their expectations were completely met and 17.6% stated that they were partially met. Self-reported refractive error quality of life improved significantly in all queried areas of life. Most frequently reported postoperative limitations were driving at night and driving in bad weather conditions. Halos were reported by 91 (90.1%) patients. CONCLUSIONS: Patient satisfaction and self-reported quality of life after refractive lens exchange with the AT LISA tri or AT LISA tri toric IOL was high. Glare and halos remain the only significant drawback of the procedure, leading to 40% of patients experiencing difficulties in night driving. Preoperative communication of these drawbacks is obligatory to avoid postoperative disappointment. [ J Refract Surg . 2021;37(11):768–774.]

Vitreous attachment sites possess an irregular non-circular shape in a significant number of eyes with VMT. Consequently, the area of traction appears inaccurately described by its horizontal VMT diameter alone. As the area of traction is important for therapeutic recommendation, our results emphasize the need for a more precise description of the area of traction in eyes with VMT.

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