![]() (E) Frequencies of DZ and LZ cells with premature stop codons. Numbers of cells sequenced are indicated. (D) Summary of results from multiple mice and experiments. The phenotype of sequenced cells with stop codons is shown to right. (C) Frequencies of Bcl2-tg SW HEL DZ cells with high and low BCR levels that carry Ighv region premature stop codons are shown (left). (C-E) SW HEL xBCL2-tg B cells were co-transferred with OT-II CD4 + T cells into WT hosts which were subsequently immunized with HEL-OVA/adjuvant and their GCs (IgD low CD95 + GL7 + ) were analyzed on day 8. Promotion of Survival Is Not Sufficient to Permit Cells with Non-Functional BCRs to Enter the LZ (A and B) Fucci2 mice with or without (WT) a BCL2 transgene (BCL2-tg) were immunized with SRBCs and analyzed day 10 (A) Frequencies of CXCR4 high CD83 low DZ cells and (B) CXCR4 high BCR(Igb) low cells in GCs (CD38 low IgD low GL7 + ). ![]() find that germinal center B cells replace surface BCRs in dark zones (DZ) and present evidence for a DZ checkpoint that prevents the accumulation of clones with non-functional BCRs, thus facilitating selection in the LZ. Somatic hypermutation is important for the generation of high-affinity antibodies, but this mutational process is also likely to negatively impact the functional integrity of B cell receptors (BCRs). Thus, BCR replacement and pre-screening in DZs prevents the accumulation of clones with non-functional receptors and facilitates selection in the LZ. Ectopic expression of the anti-apoptotic gene Bcl2 was not sufficient for cells with damaging mutations to reach the LZ, suggesting that BCR-dependent cues may actively facilitate the transition. Instead, apoptosis was triggered preferentially in late G1, a stage wherein cells with functional BCRs re-entered cell cycle or reduced surface expression of the chemokine receptor CXCR4 to enable LZ migration. We found that most GC B cells degrade pre-SHM receptors before leaving the DZ, and that B cells acquiring crippling mutations during SHM rarely reached the LZ. Accurate selection requires that cells fully replace surface B cell receptors (BCRs) following SHM, but whether this happens before LZ entry is not clear. Additionally, since changes always begin with the original RAW image rather than an intermediate JPEG version, JPEG compression related editing artifacts are avoided.Adaptive immunity involves the development of bespoke antibodies in germinal centers (GCs) through immunoglobulin somatic hypermutation (SHM) in GC dark zones (DZs) and clonal selection in light zones (LZs). ![]() Indeed, the same transformations can be easily reordered, and additional changes applied subsequently to yield further image improvements. ![]() LightZone outputs JPEG files which contain metadata references to the original image file location and a record of the transformations applied during editing.īecause the JPEG output files that LightZone creates include the entire conversion history, edits can always be undone in a new edit session, long after they were saved. By being non-destructive LightZone preserves the original "digital negative" which contains the maximum information originally captured by the camera, and allows additional images with different transformations to be produced from the original image. When LightZone edits an original digital image, a new resulting post-edit image file is created, and the original image left unaltered. LightZone is a non-destructive RAW editor. Once created, a style is easily applied to multiple images, allowing those standard camera compensations to be applied to every image before the photographer ever views or edits it. ![]() Using styles, photographers make and save their preferred compensations for each RAW image based upon camera specific characteristics. LightZone can create and apply pre-determined image transformations, called "styles," to an entire batch of pictures in a single operation. LightZone is a free, open source digital photo editor software application capable of editing JPEG and RAW files and is similar to Adobe Photoshop Lightroom. ![]()
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