In the past year attention has returned to the studies of antibody and complement in the clearance of erythrocytes from the circulation. Specific questions include the reasons for the difference between effects of IgG and IgM antibodies. IgG antibody causes splenic sequestration at low doses, IgM antibody causes hepatic sequestration. In both cases, complement is required for this effect. A second question is the complement receptors involved in such clearance mechanisms. Major findings this year include the unexpected find that on a per complement fixing site basis, IgM antibody deposits far more C3 on a target than does IgG. The kinetics of deposition are also different; C3 deposition with IgM is far faster. Once bound to the target, C3 is shed from both the IgG and the IgM coated targets at the same rate. The molecular form of C3 deposited on the target has been found to be C3bi with both IgM and IgG with very little C3b on the target. In a guinea pig model there is little evidence for the formation of C3dg in vitro on the erythrocyte surface. The fact that some C3b is deposited on the target can be shown by experiments in which sensitized cells are treated with trypsin. Trypsin is known to preferentially degrade C3bi. Once trypsinized, erythrocytes sensitized with antibody can be shown to have small amounts of C3b on their surface obscured by large amounts of C3bi. In preliminary experiments, such trypsinized cells which have released most of their C3 from the surface are cleared from the circulation in guinea pigs to the same extent as cells not treated with trypsin. These preliminary data suggest that C3b is the major opsonin causing clearance. Firming up these various points and determining the absolute number of ligands in each clinical situation is our major goal at present.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Intramural Research (Z01)
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