Submitted January 8, 2002
Accepted June 11, 2002
Anti-µ opioid receptor IgG antibodies are commonly present in serum of healthy blood donors : evidence for a role in apoptotic immune cell death
Gaetane Mace, Martial Jaume, Catherine Blanpied, Lionel Stephan, Jerome D Coudert, Philippe Druet, and Gilles Dietrich*
Oncogenesis and signaling in haematopoietic cells, INSERM U563, Toulouse, France
* Corresponding author; email: Gilles.Dietrich{at}toulouse.inserm.fr.
We have previously shown the presence of anti-human µ opioid receptor autoantibodies within IgG pools prepared from several thousands of healthy blood donors. These autoantibodies behaved agonistically due to their ability to bind to the first and the third extracellular loops of the receptor. In this study, we show that each healthy donor's serum contains anti-µ opioid receptor IgG autoantibodies exhibiting a specific activity against both the first and the third extracellular loops of the receptor. Because of the inability of IgG to cross the blood-brain barrier, we investigated the consequences of the expression of anti-human µ opioid receptor autoantibodies on immune cells. By analogy to morphine effects, we investigated the ability of antibodies to sensitize splenocytes to Fas (CD95)-mediated apoptosis. We took advantage of the high sequence homology between mouse and human µ opioid receptor extracellular loops to estimate the effect on mouse splenocytes of anti-human µ opioid receptor antibodies raised by immunizing mice. Splenocytes from mice injected with µ-opioid receptor-expressing CHO cells were sensitized to Fas-mediated apoptosis while those from mice injected with CHO cells or PBS were not. Similar sensitization to Fas-mediated apoptosis was observed in splenocytes from mice passively transferred either with IgG from mice previously immunized against µ-opioid receptor-expressing CHO cells, or with IgG directed against the first and the third extracellular loops of the receptor. Taken together, our data show that anti-µ-opioid receptor autoantibodies are commonly expressed in healthy humans and could participate to the control of lymphocyte homeostasis by promoting Fas-mediated apoptosis.
