BAFF and BAFF-Receptor in B Cell Selection and Survival

The BAFF-receptor (BAFFR) is encoded by the TNFRSF13C gene and is one of the main pro-survival receptors in B cells. Its function is impressively documented in humans by a homozygous deletion within exon 2, which leads to an almost complete block of B cell development at the stage of immature/transitional B cells. The resulting immunodeficiency is characterized by B-lymphopenia, agammaglobulinemia, and impaired humoral immune responses. However, different from mutations affecting pathway components coupled to B cell antigen receptor (BCR) signaling, BAFFR-deficient B cells can still develop into IgA-secreting plasma cells. Therefore, BAFFR deficiency in humans is characterized by very few circulating B cells, very low IgM and IgG serum concentrations but normal or high IgA levels

Trust As A Precursor Or Outcome Of Relational Norm Development: A Cross-Cultural Comparison Of US And Hungarian Managers

This study proposes and tests a model delineating relational norms and their relationship with the construct Trust and compares the results across two culture groups.  The norms of Solidarity, Flexibility, and Mutuality are proposed as precursors to the formation of Trust.  SEM results confirm two opposing models for U.S. and Hungarian respondents.  Relational Norms have a strong positive relationship with formation of Trust for the Hungarian respondents, acting as a precursor of Trust.  Whereas, the relationship between trust and the relational norms is weak for the U.S. respondents, and indicates that Trust is a precursor to the formation of Relational Norms

MRI of the lung (3/3)-current applications and future perspectives

BACKGROUND: MRI of the lung is recommended in a number of clinical indications. Having a non-radiation alternative is particularly attractive in children and young subjects, or pregnant women. METHODS: Provided there is sufficient expertise, magnetic resonance imaging (MRI) may be considered as the preferential modality in specific clinical conditions such as cystic fibrosis and acute pulmonary embolism, since additional functional information on respiratory mechanics and regional lung perfusion is provided. In other cases, such as tumours and pneumonia in children, lung MRI may be considered an alternative or adjunct to other modalities with at least similar diagnostic value. RESULTS: In interstitial lung disease, the clinical utility of MRI remains to be proven, but it could provide additional information that will be beneficial in research, or at some stage in clinical practice. Customised protocols for chest imaging combine fast breath-hold acquisitions from a "buffet" of sequences. Having introduced details of imaging protocols in previous articles, the aim of this manuscript is to discuss the advantages and limitations of lung MRI in current clinical practice. CONCLUSION: New developments and future perspectives such as motion-compensated imaging with self-navigated sequences or fast Fourier decomposition MRI for non-contrast enhanced ventilation- and perfusion-weighted imaging of the lung are discussed. Main Messages • MRI evolves as a third lung imaging modality, combining morphological and functional information. • It may be considered first choice in cystic fibrosis and pulmonary embolism of young and pregnant patients. • In other cases (tumours, pneumonia in children), it is an alternative or adjunct to X-ray and CT. • In interstitial lung disease, it serves for research, but the clinical value remains to be proven. • New users are advised to make themselves familiar with the particular advantages and limitations

Recurrent respiratory tract infections (RRTI) in the elderly: A late onset mild immunodeficiency?

Transplantation and immunomodulatio

A distinct CD38+CD45RA+ population of CD4+, CD8+, and double-negative T cells is controlled by FAS.

The identification and characterization of rare immune cell populations in humans can be facilitated by their growth advantage in the context of specific genetic diseases. Here, we use autoimmune lymphoproliferative syndrome to identify a population of FAS-controlled TCRαβ+ T cells. They include CD4+, CD8+, and double-negative T cells and can be defined by a CD38+CD45RA+T-BET- expression pattern. These unconventional T cells are present in healthy individuals, are generated before birth, are enriched in lymphoid tissue, and do not expand during acute viral infection. They are characterized by a unique molecular signature that is unambiguously different from other known T cell differentiation subsets and independent of CD4 or CD8 expression. Functionally, FAS-controlled T cells represent highly proliferative, noncytotoxic T cells with an IL-10 cytokine bias. Mechanistically, regulation of this physiological population is mediated by FAS and CTLA4 signaling, and its survival is enhanced by mTOR and STAT3 signals. Genetic alterations in these pathways result in expansion of FAS-controlled T cells, which can cause significant lymphoproliferative disease

MRI of the lung (2/3). Why … when … how?

Background Among the modalities for lung imaging, proton magnetic resonance imaging (MRI) has been the latest to be introduced into clinical practice. Its value to replace X-ray and computed tomography (CT) when radiation exposure or iodinated contrast material is contra-indicated is well acknowledged: i.e. for paediatric patients and pregnant women or for scientific use. One of the reasons why MRI of the lung is still rarely used, except in a few centres, is the lack of consistent protocols customised to clinical needs. Methods This article makes non-vendor-specific protocol suggestions for general use with state-of-the-art MRI scanners, based on the available literature and a consensus discussion within a panel of experts experienced in lung MRI. Results Various sequences have been successfully tested within scientific or clinical environments. MRI of the lung with appropriate combinations of these sequences comprises morphological and functional imaging aspects in a single examination. It serves in difficult clinical problems encountered in daily routine, such as assessment of the mediastinum and chest wall, and even might challenge molecular imaging techniques in the near future. Conclusion This article helps new users to implement appropriate protocols on their own MRI platforms. Main Messages • MRI of the lung can be readily performed on state-of-the-art 1.5-T MRI scanners. • Protocol suggestions based on the available literature facilitate its use for routine • MRI offers solutions for complicated thoracic masses with atelectasis and chest wall invasion. • MRI is an option for paediatrics and science when CT is contra-indicate

Long-Lived Plasma Cells and Memory B Cells Produce Pathogenic Anti-GAD65 Autoantibodies in Stiff Person Syndrome

Stiff person syndrome (SPS) is a rare, neurological disorder characterized by sudden cramps and spasms. High titers of enzyme-inhibiting IgG autoantibodies against the 65 kD isoform of glutamic acid decarboxylase (GAD65) are a hallmark of SPS, implicating an autoimmune component in the pathology of the syndrome. Studying the B cell compartment and the anti-GAD65 B cell response in two monozygotic twins suffering from SPS, who were treated with the B cell-depleting monoclonal anti-CD20 antibody rituximab, we found that the humoral autoimmune response in SPS is composed of a rituximab-sensitive part that is rapidly cleared after treatment, and a rituximab-resistant component, which persists and acts as a reservoir for autoantibodies inhibiting GAD65 enzyme activity. Our data show that these potentially pathogenic anti-GAD65 autoantibodies are secreted by long-lived plasma cells, which may either be persistent or develop from rituximab-resistant memory B lymphocytes. Both subsets represent only a fraction of anti-GAD65 autoantibody secreting cells. Therefore, the identification and targeting of this compartment is a key factor for successful treatment planning of SPS and of similar autoimmune diseases

The population biology and evolutionary significance of Ty elements in Saccharomyces cerevisiae

The basic structure and properties of Ty elements are considered with special reference to their role as agents of evolutionary change. Ty elements may generate genetic variation for fitness by their action as mutagens, as well as by providing regions of portable homology for recombination. The mutational spectra generated by Ty 1 transposition events may, due to their target specificity and gene regulatory capabilities, possess a higher frequency of adaptively favorable mutations than spectra resulting from other types of mutational processes. Laboratory strains contain between 25–35 elements, and in both these and industrial strains the insertions appear quite stable. In contrast, a wide variation in Ty number is seen in wild isolates, with a lower average number/genome. Factors which may determine Ty copy number in populations include transposition rates (dependent on Ty copy number and mating type), and stabilization of Ty elements in the genome as well as selection for and against Ty insertions in the genome. Although the average effect of Ty transpositions are deleterious, populations initiated with a single clone containing a single Ty element steadily accumulated Ty elements over 1,000 generations. Direct evidence that Ty transposition events can be selectively favored is provided by experiments in which populations containing large amounts of variability for Ty1 copy number were maintained for ∼100 generations in a homogeneous environment. At their termination, the frequency of clones containing 0 Ty elements had decreased to ∼0.0, and the populations had became dominated by a small number of clones containing >0 Ty elements. No such reduction in variability was observed in populations maintained in a structured environment, though changes in Ty number were observed. The implications of genetic (mating type and ploidy) changes and environmental fluctuations for the long-term persistence of Ty elements within the S. cerevisiae species group are discussed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/42799/1/10709_2004_Article_BF00133718.pd