Follicular helper (TFH) cells provide crucial signals to germinal center B cells undergoing somatic hypermutation and selection that results in affinity maturation. Tight control of TFH numbers maintains self-tolerance. We describe a population of Foxp3+Blimp-1+CD4+ T cells constituting 10-25% of the CXCR5highPD-1highCD4+ T cells found in germinal center after immunization. These follicular regulatory T cells (TFR) share phenotypic characteristics with TFH and conventional Foxp3+ regulatory T cells (Treg) yet are distinct from either. Similar to TFH cells, TFR development depends on Bcl-6, SAP, CD28 and B cells; however TFR originate from thymic-derived Foxp3+ precursors, not naïve or TFH cells. TFR are suppressive in vitro and limit TFH and germinal center B cell numbers in vivo. In the absence of TFR, an outgrowth of non-antigen-specific B cells in germinal centers leads to fewer antigen-specific cells. Thus, Treg cells use the TFH differentiation pathway to produce specialized suppressor cells that control the germinal center response.

During T cell–dependent responses, B cells can either differentiate extrafollicularly into short-lived plasma cells or enter follicles to form germinal centers (GCs). Interactions with T follicular helper (Tfh) cells are required for GC formation and for selection of somatically mutated GC B cells. Interleukin (IL)-21 has been reported to play a role in Tfh cell formation and in B cell growth, survival, and isotype switching. To date, it is unclear whether the effect of IL-21 on GC formation is predominantly a consequence of this cytokine acting directly on the Tfh cells or if IL-21 directly influences GC B cells. We show that IL-21 acts in a B cell–intrinsic fashion to control GC B cell formation. Mixed bone marrow chimeras identified a significant B cell–autonomous effect of IL-21 receptor (R) signaling throughout all stages of the GC response. IL-21 deficiency profoundly impaired affinity maturation and reduced the proportion of IgG1+ GC B cells but did not affect formation of early memory B cells. IL-21R was required on GC B cells for maximal expression of Bcl-6. In contrast to the requirement for IL-21 in the follicular response to sheep red blood cells, a purely extrafollicular antibody response to Salmonella dominated by IgG2a was intact in the absence of IL-21.

The evolution of increased competitive ability (EICA) hypothesis provides a compelling explanation for the success of invasive species. It contends that because alien plants have escaped their coevolved natural enemies, selection pressures favor a diversion of resources from herbivore defense to traits that confer increased competitive ability. Here, we provide evidence for EICA in the noxious grassland invader Lespedeza cuneata, by comparing the ancestral genotype introduced to North America in 1930 with modern‐day invasive (North American) and native (Japanese) genotypes. We found that the invasive genotype was a better competitor than either the native or the ancestral genotype. Further, the invasive genotype exhibited greater induced resistance but lower constitutive resistance than the ancestral and native genotypes. Our results suggest that selection has played a pivotal role in shaping this invasive plant species into a more aggressive, but less constitutively defended competitor.

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Plant communities in the verges of major roadways (roadsides) are similar to those of abandoned farm fields undergoing succession (oldfields). However, roadsides are subject to distinctive stresses. Here, we look at local adaptation in Hesperis matronalis L. to salinity and manganese (Mn). Plants collected from three roadside and three oldfield populations were grown in a greenhouse under controlled, high-salinity, and high-Mn conditions, and several life history traits were measured. In addition, we imposed a density treatment after vernalization. Mortality was high in both the salt (43% survival) and Mn treatments (53% survival) compared with the control (71% survival). Distinct family, population, and site variation was found in measures of plant size. There were also family-level differences in response to soil treatments. However, none of our results were consistent with local adaptation. In general, larger plants were more likely to bolt, and oldfield plants were less likely to bolt than roadside plants in all treatments (in the low-density treatment, 56% of roadside plants had bolted compared with only 16% of oldfield plants). We found that the high-density treatments resulted in earlier bolting and longer internodes, a result consistent with the shade avoidance hypothesis.Résumé : Les communautés végétales en marge des routes principales (bords de route) sont semblables à celles des terres agricoles abandonnées en succession (vieilles prairies). Cependant, les bords de route sont soumis à des stress particuliers. Les auteurs examinent l'adaptation locale de l'Hesperis matronalis L. à la salinité et au manganèse (Mn). Ils ont cultivé en serres, sous des conditions contrôlées impliquant de fortes teneurs en sel et en manganèse, des plantes récoltées sur les bords de trois routes et à partir de trois populations de vieilles prairies, et ont mesuré plusieurs aspects de leur cycle vital. De plus, ils ont imposé un traitement de densité après vernalisation. La mortalité est élevée dans les deux traitements avec le sel (43%) et le Mn (53%), comparativement aux témoins (71%). On observe une variation au niveau de la famille, de la population et du site, dans les mesures des dimensions des plantes. Il y a également des différences au niveau de la famille en réaction aux traitements du sol. Cependant, aucun des résultats n'est congru avec une adaptation locale. En général, les grandes plantes sont plus susceptibles de monter en graines, et les plantes de vieilles prairies sont moins susceptibles de le faire que les plantes des bords de route, quel que soit le traitement (dans le traitement à faible densité, 56% des plantes de bords de route ont monté à la graine, comparativement à seulement 16% pour les plantes de vieilles prairies). On constate que les traitements à haute densité conduisent à une montée en graines plus hâtive et des entrenoeuds plus longs, un résultat qui concorde avec l'hypothèse d'intolérance à l'ombre.

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Previous studies have demonstrated that plants collected as seeds from roadside populations of Dipsacus fullonum L. subsp sylvestris (Huds.) Claphamare more tolerant of high salinity, low osmotic potentials, and hypoxia during juvenile growth stages than those from oldfield populations. However, it is unclear how tolerance to these abiotic stressors translates into performance in the roadside environment. Here, we conducted a reciprocal transplant experiment between oldfield and roadside environments. Seeds from three roadside and three oldfield populations were planted into oldfield and roadside sites in late fall. Throughout the spring and summer, the survivorship and size of the seedlings were monitored to examine differences in performance in the two habitats. We also assessed the relation between performance in the field and previous in vitro measures of salt and drought tolerance of each population. A drought caused high mortality levels in the oldfield and roadside. Individuals from roadside populations did not exhibit increased growth or survivorship in the roadside environment. In the early months of seedling growth, neither salt nor drought tolerance were significantly correlated with performance in the roadside during seedling establishment. Rather, during these early months, the average size of individuals in each population in the field was positively correlated with the population’s average seed mass, indicating that maternal provisioning had a greater impact than tolerance to particular environmental stresses during the juvenile stages of development. However, later in the summer, after the drought began, the average size of individuals from each population in the field was positively correlated with that population’s average drought tolerance.

Introduction Professional identity development is a central aim of medical education, which has been disrupted during COVID-19. Yet, no research has qualitatively explored COVID-19’s impact across institutions or countries on medical students’ identities. Kegan proposes a cognitive model of identity development, where ‘disorientating dilemmas’ prompt student development. Given the potential of COVID-related disruption to generate disorientating dilemmas, the authors investigated the ways in which COVID-19 influenced students’ identity development. Methods The authors conducted an international qualitative study with second year medical students from Imperial College London, and third year students from Melbourne Medical School. Six focus groups occurred 2020–2021, with three to six students per group. Authors analysed data using reflexive thematic analysis, applying Kegan’s model as a sensitising theoretical lens. Results COVID-19 has resulted in a loss of clinical exposure, loss of professional relationships, and a shift in public perception of physicians. Loss of exposure to clinical practice removed the external validation from patients and seniors many students depended on for identity development. Students’ experiences encouraged them to assume the responsibilities of the profession and the communities they served, in the face of conflicting demands and risk. Acknowledging and actioning this responsibility facilitated identity development as a socially responsible advocate. Conclusions Educators should consider adapting medical education to support students through Kegan’s stages of development. Measures to foster relationships between students, patients, and staff are likely necessary. Formal curricula provisions, such as spaces for reflection and opportunities for social responsibility, may aid students in resolving the conflict many have recently experienced.