Optimality of mutation and selection in germinal centers

The population dynamics theory of B cells in a typical germinal center could play an important role in revealing how affinity maturation is achieved. However, the existing models encountered some conflicts with experiments. To resolve these conflicts, we present a coarse-grained model to calculate the B cell population development in affinity maturation, which allows a comprehensive analysis of its parameter space to look for optimal values of mutation rate, selection strength, and initial antibody-antigen binding level that maximize the affinity improvement. With these optimized parameters, the model is compatible with the experimental observations such as the ~100-fold affinity improvements, the number of mutations, the hypermutation rate, and the "all or none" phenomenon. Moreover, we study the reasons behind the optimal parameters. The optimal mutation rate, in agreement with the hypermutation rate in vivo, results from a tradeoff between accumulating enough beneficial mutations and avoiding too many deleterious or lethal mutations. The optimal selection strength evolves as a balance between the need for affinity improvement and the requirement to pass the population bottleneck. These findings point to the conclusion that germinal centers have been optimized by evolution to generate strong affinity antibodies effectively and rapidly. In addition, we study the enhancement of affinity improvement due to B cell migration between germinal centers. These results could enhance our understandings to the functions of germinal centers.Comment: 5 figures in main text, and 4 figures in Supplementary Informatio

Podoplanin expression in oral leukoplakia: prognostic value and clinicopathological implications

Oral Diseases (2012) 18, 692699 Objectives: Current clinicopathological parameters cannot predict the risk of malignant transformation in oral leukoplakia sufficiently. Recent studies have shown that podoplanin is expressed in oral cancer and precancerous lesions. The aim of our study was to assess whether podoplanin expression in pretreatment biopsies could serve as a biomarker to predict the risk of malignant transformation in patients with oral leukoplakia. Materials and Methods: In this retrospective study, podoplanin expression was analysed in 60 patients with previously untreated oral leukoplakia by immunohistochemistry. We investigated the associations between podoplanin expression and various clinicopathological variables including oral cancer-free survival (OCFS) and the SIN-classification. Results: The chi-square-test revealed that high expression of podoplanin in pretreatment biopsies was associated with malignant transformation (P = 0.003) and increasing SIN-classification (P = 0.009). In univariate analysis, podoplanin expression in oral leukoplakia had a significant impact on OCFS (P = 0.009). The 5-year OCFS rate decreased from 100% for patients with no podoplanin expression to 41.7% for patients with the highest level of podoplanin expression. Conclusion: Although podoplanin expression and the SIN-classification served as factors to predict malignant transformation in patients with oral leukoplakia in univariate analysis, no significant impact was found for both factors in multivariate analysis

Preridiniopsis Kevei SP. nov., A new freshwater dinoflagellate species (peridiniceae, dinophyta) from Hungary

This paper reports results from light and scanning electron microscopic study of a freshwater dinoflagellate considered as a new species for the science, Peridiniopsis keveisp. nov. It was found during the last ten years in different lake, rivers, canals in Hungary and some European countries. it frequently appeared as a water-bloom forming species. The theca morphology and and plate structure analysis of this dinoflagellate established its identity as a new species. P. kevei Grigorszky et Vasas is discussed in the paper in comparsion with related taxa, moreover data about its occurrence and ecology

Antibody evolution constrains conformational heterogeneity by tailoring protein dynamics

The evolution of proteins with novel function is thought to start from precursor proteins that are conformationally heterogeneous. The corresponding genes may be duplicated and then mutated to select and optimize a specific conformation. However, testing this idea has been difficult because of the challenge of quantifying protein flexibility and conformational heterogeneity as a function of evolution. Here, we report the characterization of protein heterogeneity and dynamics as a function of evolution for the antifluorescein antibody 4-4-20. Using nonlinear laser spectroscopy, surface plasmon resonance, and molecular dynamics simulations, we demonstrate that evolution localized the Ab-combining site from a heterogeneous ensemble of conformations to a single conformation by introducing mutations that act cooperatively and over significant distances to rigidify the protein. This study demonstrates how protein dynamics may be tailored by evolution and has important implications for our understanding of how novel protein functions are evolved