Germinal center versus extrafollicular responses in systemic autoimmunity: Who turns the blade on self?

Spontaneously formed germinal centers (GCs) have been reported in most mouse models of human autoimmune disease and autoimmune patients, and have long been considered a source of somatically-mutated and thus high affinity autoantibodies, but their role in autoimmunity is becoming increasingly controversial, particularly in the context of systemic autoimmune diseases like lupus. On the one hand, there is good evidence that some pathogenic lupus antibodies have acquired somatic mutations that increase affinity for self-antigens. On the other hand, recent studies that have genetically prevented GC formation, suggest that GCs are dispensable for systemic autoimmunity, pointing instead to pathogenic extrafollicular (EF) B-cell responses. Furthermore, several lines of evidence suggest germinal centers may in fact be somewhat protective in the context of autoimmunity. Here we review how some of the conflicting evidence arose, and current views on the role of GCs in autoimmunity, outlining mechanisms by which GC may eliminate self-reactivity. We also discuss recent advances in understanding extrafollicular B cell subsets that participate in autoimmunity

Supplementary document for Dataset artificial augmentation with a small number of training samples for reflectance estimation - 6281952.pdf

Supplemental 1 for additional figures and tabl

Supplementary document for Dataset artificial augmentation with a small number of training samples for reflectance estimation - 6277046.pdf

Supplemental documen

Leaf traits of heading Chinese cabbage and non-heading Chinese cabbage and their recombination lines.

<p>Leaf traits of heading Chinese cabbage and non-heading Chinese cabbage and their recombination lines.</p

QTLs of 6 heading traits in two years.

<p>QTLs of 6 heading traits in two years.</p

Precise locations of three QTLs and candidate genes.

<p>Curves indicate chromosomal locations and LOD values of detected QTLs. Names and phenotypic effect (R2) of the QTLs are indicated. Recombination bins near the LOD peaks of the QTL are illustrated as horizontal bars with their numbers labeled inside. Shaded bin overlaps the LOD peak of a QTL. The portion of a curve and corresponding bins defining the 95% confidence interval of a QTL are bracketed by two lines. The relative physical position of a candidate gene in the bin is indicated by an arrow head.</p

Data of head traits in the parents and the RIL population.

<p>Data of head traits in the parents and the RIL population.</p

Additional file 1: of HTT2 promotes plant thermotolerance in Brassica rapa

Table S1. Primers for expression analysis of qRT-PCR, cDNA cloning of HTT2, and identification of HPT gene in transgenic plants. (DOCX 20 kb

Linkage relationship between the QTLs for head traits.

<p>The names of QTLs are described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0076059#pone-0076059-t003" target="_blank">Table 3</a>. The black and grey arrow heads indicate the locations of QTLs in 2011 and 2012, respectively. The locations of the QTLs for qTr and qLW in the two years are the same and indicated by white arrow heads.</p

Recombination map and linkage map.

<p>(A) Recobination map of 150 RILs; (B) Pairwise recombination fractions and LOD scores; (C) Genetic linkage map after filtering markers that recombination rates higher than 20%.</p