RE: Mouse NK1.1 cells in peripheral blood

From: Rick A. Bright (rbright@emory.edu)
Date: Thu Apr 19 2001 - 08:47:12 EST


Thank you all for responding so quickly to my issues.  In summary, I have
learned that I did not read the PharMingen catalog closely enough to know
that the NK1.1 is NOT expressed in BALB/c mice; I should have used the DX5
Pan-NK mAB instead (it should be here today to use in the last timepoint of
this expt.).

It has also been recommended that I use BSA instead of FBS in my FACS Buffer
due to the variability in FBS reactivity and between Lots of FBS.

A few of you suggested that I use 2% paraformaldehyde in my fixing solution
and to make it fresh daily.  I have heard mixed reviews on the stability of
this buffer.  Some say that they make a lot, keep it in an amber bottle at
4degrees and it keeps for weeks.  I have been making it fresh weekly and
storing it at 4 degrees in an amber bottle.  I still don't have a consensus
on this matter.

There are additional thoughts on the fact that I should not be using CD95
(Fas) and an indicator for cells undergoing apoptosis.  I am looking more
closely into this.

Thank you for your great help.  I received many rapid responses and they
were in time to make a quick change and not lose valuable time and data.

Rick

-----Original Message-----
From: Rick A. Bright [mailto:rbright@emory.edu]
Sent: Wednesday, April 18, 2001 12:08 AM
To: cyto-inbox
Subject: Mouse NK1.1 cells in peripheral blood



First, I want to thank the many of you who wrote to help me figure out my
first FACS protocol.  It is working very nicely and only took me one failed
attempts (which wasn't a failure at all because I learned from the several
mistakes), and has worked ever since.  I am having a couple of problems
overall that I hope someone can help me resolve.

To remind everyone:  I am collecting whole blood from female BALB/c mice
(7-8 w.o.) and using 50ul to determine the blood cell count and look for an
upregulation of an apoptotic marker, CD95 (Fas).  My tubes contain (all
PharMingen):
1) CD3-PerCP, CD4-PE, CD8-APC, CD95-FITC; 2)CD3-PerCP, CD19-PE,
Ly-6G(Neuts)-APC, NK1.1-FITC; and 3) CD3-PerCp, CD19-PE, CD11b(Mac1)-APC,
CD95-FITC  I also use 5ul of Fc Block in each tube for 5 minutes prior to
adding the antibodies and I use the BD FACSlyse buffer (2mL for 7-10min at
rt).  I keep everything in the dark at all times and besides the lyse step,
all is done on ice.  I have PBS, FBS and Azide in my FACS buffer and I fix
the cells in a 500ul vol of 1% paraformaldehyde solution after 2 washes with
FACS buffer (I do not wait o/n to read the cells, however, I read right
away).

First issue:  I tend to lose the CD3-PerCp color rather quickly, especially
on the double-positive with CD4-PE.  Sometimes all of the CD4 are also CD3+
and sometimes they sit down on the PE axis.  However, the CD3-PerCp/CD8-APC
seem to be more stable as double-positives.  Once, I read the cells
immediately and all of the CD4+ were also CD3+, the next day, I checked
again and the same #/% of CD4+ cells were collected, but they were not
double pos for CD3 and were back down to the CD4 axis.


Second issue:  I cannot find any NK cells.  I know that they should fall
into the area that is slightly larger and slightly more granular than
lymphocytes and I have read that the population can be as high as 5-10% of
peripheral blood cells.  Does this sound right?  Is anyone currently looking
at NK cells in mice?  I am using the NK1.1 antibody from PharMingen at a
1:10 dilution, using 25 ul of the diluted antibodies in each tube with 50ul
of whole blood and staining for 30min on ice.  I check everywhere, even
without any gates and see nothing pop up in the LR quad of my FL1 channel.


Third issue (never say final, right?):  When collecting events, I have taken
off all thresholds to collect in the full window.  However, as you know, I
get many junk events that tends to quickly reduce the number of "good"
events that I want.  So, instead of setting thresholds (in case my cells
change during apoptosis or other forms of death and are not rejects behind
the threshold), I gated a region that goes all the way around the perimeter
of the window and makes an inward loop over the xy point of axis.  I still
acquire and save all events, but have the count go up to 10000 events within
the gated region (which omits that massive clump of debris at the axes.  So,
in a way, I am trying to collect 10K events, excluding the debris, but still
collecting data on the debris.  This brought my valid lymphocytes from a
count of 800 to a count of thousands.


Any thoughts on each or any of these questions would be most helpful and
appreciated.  I am very grateful for the expertise among this membership and
will soon be in a better position to cross to the other side and give as
much advise as I now borrow.  Thank you.

Rick



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