Release of endogenous C3b inactivator from lymphocytes in response to triggering membrane receptors for beta 1H globulin.
Human bone marrow-derived lymphocytes and cells from B lymphoblastoid lines were shown to have specific membrane receptors for beta 1H globin. Lymphocytes responded to the presence of beta 1H by releasing endogenously-synthesized C3b-inactivator. Very little spontaneous release of C3b-inactivator occurred in the absence of beta 1H. beta 1H-treated lymphocytes that either lacked complement receptor type one (CR1, the C4b-C3b receptor) or had their CR1 blocked with Fab'-anti-CR1 formed rosettes with C3b-coated sheep erythrocytes (EC3b) by adherence to complement receptor type two (CR2, the C3d-C3bi receptor). The mechanism of the beta 1H-induced EC3b rosette formation was shown to involve the release of lymphocyte C3b-inactivator that cleaved bound C3b into C3bi forming EC3bi. This lymphocytes-generated EC3bi then bound to CR2, forming rosettes. beta 1H-induced EC3b rosettes were completely inhibited by the presence of either anti-C3b-inactivator, F(ab')2-anti-CR2, Fab-anti-C3c, or Fab-anti-C3d, but were unaffected by the presence of fluid-phase concentrations of beta 1H up to 5.5 mg/ml or Fab'-anti-CR1. Analysis by sodium dodecyl sulfate polyacrylamide gel electrophoresis and fluorography demonstrated that cell-free supernates of beta 1H-treated lymphocytes cleaved 3H-labeled C3b on EC3b into C3bi. Inhibition studies with chelating agents and sodium azide suggested that the release of C3b inactivator might involve a calcium and energy-dependent transport of this enzyme across the membranes of beta 1H-triggered cells. Because plasma beta 1H and C3b-inactivator are known to have important functions in the distinction of alternative pathway-activating substances from normal tissue, it is possible that this beta 1H receptor-C3b-inactivatory releasing system in lymphocytes may have an analogous function.
D001402:B-Lymphocytes / Q000378:metabolism*; D002460:Cell Line; D003180:Complement C3b Inactivator Proteins / Q000378:metabolism*; D017242:Complement Factor H; D006801:Humans; D011951:Receptors, Complement / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000378:metabolism*; D012397:Rosette Formation
C493495:CFH protein, human; D003180:Complement C3b Inactivator Proteins; D011951:Receptors, Complement; D011971:Receptors, Immunologic; D017242:Complement Factor H