See also Figure S5.Īntibody affinity maturation occurs in germinal centers (GCs) through iterative rounds of somatic hypermutation and proliferation in dark zones (DZs) and selection in light zones (LZs). Analysis was performed using an unpaired two-tailed Student's t test, ***p < 0.001. Data in (A) and (B) are pooled from 3 experiments with each point representing a single mouse. Numbers are means from two independent experiments which are shown separately in Figure S5F.
(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. I can't justify the cost of all the tools I'd need under windows, so I've stuck with Linux.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).
Lightzone wont open in windows xp software#
I use Linux mainly because I'm a geek, and secondarily because I'm running a part time photography business and want to 'own' all my software I use for that. The only things I've found I can't do under Linux are simple/quick AV slideshows (photos2exe, photostory etc) _simple_ HDR work (Photomatix) and shooting tethered (Canon Eos Capture or DPP, DPP is far better.)
(I keep everything)Īnd Inkscape for vector work when I need to.
Lightzone wont open in windows xp archive#
I use Hugin and panorama tools for panoramas.Īnd gthumb for doing select/pick of photos for the bulk of mywork, and archive them into a gallery running menalto gallery running on a local server, with per-job headers and per photo captions if I've collected them. I use imagemagik, jhead and netpbmtools for scripted image handling, to do watermarks on bulk jobs etc. (When, o when will they release native 16bit gimp?) I use gimp for editing, dcraw plugin for raw import if I feel the urge, cinepaint for doing 16bit editing when I really need some extra gradation/detail. Havn't entered anything for a while, but I'm using Linux for all my photography apart from shooting tethered on an XP laptop using Canon DPP occasionally.
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