shifted backgrounds with fluorescent protein expression

From: Phil Marder (mr_redram@hotmail.com)
Date: Mon Oct 22 2001 - 14:21:12 EST


Here's a tough one that I can't figure out.....

A colleague of mine transiently transfected HEK-293 cells with message for
CMV-driven yellow (Topaz) fluorescence protein.  He brought the cells up for
me to analyze on our cytometer.   I used 488 excitation and read out both
FL1 and FL2 log signals.  The gains were set as usual, so that the
sham-transfected control (auto)fluorescence was set within the first decade.
  For the Topaz transfected cells, I observed about 40% of the cells
fluorescing under the microscope.  But when I analyzed them on the
cytometer, EVERYTHING was shifted to the right, including the negative
subpopulation of the transfected sample.  The ~%40 percent positive subset
was clearly discernible from the "right-shifted" negative population.

Of course this suggested that there was an autofluorescence issue, but this
was clearly not observed on the microscope using similar filter
arrangements.

A couple of other issues for you to consider with this experiment:
1- the "positive" cells were incredibly bright on the microscope
2- when we mixed the sham-transfected with the test cells, the negative peak
of the sham-transfected cells moved right as well!!

What is going on here?   Is there such a thing as a "lantern" effect of very
bright cells in close proximately with negatives?  Is fluorescent
subcellular debris confounding my light scatter gating?   Please give me
your explanations because I've not seen this phenomenon before in flow.

Phil Marder
Lilly Research Labs

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