Binding of immune complexes to erythrocyte CR1 (CD35): Difference in requirement of classical pathway components and indication of alternative pathway-mediated binding in C2-deficiency

Deficiency of complement components within the classical pathway is associa ted with increased risk for immune complex disease. However, C2-deficient i ndividuals often have a mild disease and about 50% are healthy. To study th e importance of the different components for immune complex clearance, bovi ne serum albumin (BSA)/anti-BSA complexes were opsonized in human serum and the binding to erythrocyte complement receptor type 1 (CR1, CD35) was meas ured in vitro. In C2-depleted serum the complexes were opsonized and bound to CR1 but the reaction needed a longer opsonization time than in normal hu man serum (NHS). In contrast, serum reagent lacking C1q, C4 or C3 did not p romote binding in this assay system. We also demonstrated that elevated lev els of factor B could restore binding of complexes to erythrocytes in C2-de pleted serum via alternative pathway activation. These results indicate tha t in spite of lack of a complete classical pathway, C2-deficient individual s could retain some immune complex opsonizing activity via the alternative pathway. This finding could contribute to the understanding of differences in association between complement deficiency and immune-complex disease.