The Human Thymus Is Enriched for Autoreactive B Cells

The human thymus has been shown to host B cells, which have been implicated in presentation of autoantigens for negative selection of T cell progenitors. Although these Ags are thought to be taken up through their surface Igs, data on thymic Ig gene repertoires are limited and reactivity to autoantigens has not been demonstrated. We therefore studied the Ig gene repertoires and reactivity to autoantigens of single-sorted B cells from pediatric thymus, and compared these with mature B cells from fetal and pediatric bone marrow. Nearly all B cells in thymus were mature and displayed an Ig gene repertoire that was similar to pediatric bone marrow. Fetal mature B cells predominantly used proximal V, D, and J genes, and their Abs were highly reactive to dsDNA. In contrast, thymic B cells were enriched for autoreactive clones that showed increased specificity to peptide autoantigens. Thus, most B cells in the thymus are resident rather than developing, and are enriched for autoantigen binding. These features support current models for a role of thymic B cells in presentation of autoantigens to developing T cells during negative selection

Hugo Who? G. F. Arnold’s Alternative Early Approach to Psychology and Law

Hugo Münsterberg is widely regarded as the founder of the discipline of psychology and law, and the publication of his book On the Witness Stand (1908) is considered the signal event in its founding. However, numerous other researchers were conducting and publishing research on psycholegal topics in the late 1800s and early 1900s, and at least one other book on psychology and law— G. F. Arnold’s Psychology Applied to Legal Evidence and Other Constructions of Law (1906)—appeared prior to the publication of Münsterberg’s work. The present paper contrasts these two seminal publications, focusing on their relevance to the “basic-versus-applied” debate in contemporary eyewitness memory research and exploring reasons why Münsterberg has been so influential while Arnold has been largely ignored

Differential effects of Cytomegalovirus carriage on the immune phenotype of middle-aged males and females

The elderly population is more susceptible to infections as a result of an altered immune response, commonly referred to as immunosenescence. Cytomegalovirus (CMV)-infection associated changes in blood lymphocytes are known to impact this process, but the interaction with gender remains unclear. Therefore, we analysed the effects and interaction of gender and CMV on the absolute numbers of a comprehensive set of naive and memory T- and B-cell subsets in people between 50 and 65 years of age. Enumeration and characterisation of lymphocyte subsets by flow cytometry was performed on fresh whole blood samples from 255 middle-aged persons. CMV-IgG serostatus was determined by ELISA. Gender was a major factor affecting immune cell numbers. CMV infection was mainly associated with an expansion of late-differentiated T-cell subsets. CMV+ males carried lower numbers of total CD4+, CD4+ central memory (CM) and follicular helper T-cells than females and CMV-males. Moreover, CMV+ males had significantly lower numbers of regulatory T (Treg)-cells and memory B-cells than CMV+ females. We here demonstrate an interaction between the effects of CMV infection and gender on T-and B-cells in middle-aged individuals. These differential effects on adaptive immunity between males and females may have implications for vaccination strategies at middle-age

Pre-post synaptic alignment through neuroligin-1 tunes synaptic transmission efficiency

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B-Cell Dysregulation in Crohn's Disease Is Partially Restored with Infliximab Therapy

Background B-cell depletion can improve a variety of chronic inflammatory diseases, but does not appear beneficial for patients with Crohn's disease. Objective To elucidate the involvement of B cells in Crohn's disease, we here performed an 'in depth' analysis of intestinal and blood B-cells in this chronic inflammatory disease. Methods Patients with Crohn's disease were recruited to study B-cell infiltrates in intestinal biopsies (n = 5), serum immunoglobulin levels and the phenotype and molecular characteristics of blood B-cell subsets (n = 21). The effects of infliximab treatment were studied in 9 patients. Results Granulomatous tissue showed infiltrates of B lymphocytes rather than Ig-secreting plasma cells. Circulating transitional B cells and CD21(low) B cells were elevated. IgM memory B cells were reduced and natural effector cells showed decreased replication histories and somatic hypermutation (SHM) levels. In contrast, IgG and IgA memory B cells were normally present and their Ig gene transcripts carried increased SHM levels. The numbers of transitional and natural effector cells were normal in patients who responded clinically well to infliximab. Conclusions B cells in patients with Crohn's disease showed signs of chronic stimulation with localization to granulomatous tissue and increased molecular maturation of IgA and IgG. Therapy with TNF-alpha-blockers restored the defect in IgM memory B-cell generation and normalized transitional B-cell levels, making these subsets candidate markers for treatment monitoring. Together, these results suggest a chronic, aberrant B-cell response in patients with Crohn's disease, which could be targeted with new therapeutics that specifically regulate B-cell function