THE ROLE OF COMPLEMENT RECEPTOR-TYPE-1 (CR-1, CD35) IN DETERMINING THE CELLULAR-DISTRIBUTION OF OPSONIZED IMMUNE-COMPLEXES BETWEEN WHOLE-BLOOD CELLS - KINETIC-ANALYSIS OF THE BUFFERING CAPACITY OF ERYTHROCYTES

Erythrocytes (E) express complement receptor, type 1 (CR1, CD35), by w hich they bind opsonized immune complexes (IC) in competition with leu cocytes expressing higher numbers of CR1 as well as other complement- and Fc-receptors. This may prevent inappropriate activation of phagocy tic cells. We examined the distribution on whole blood cells of prefor med tetanus toroid (TT)/human anti-TT IC, opsonized in situ in 80% aut ologous serum. Binding to E occurred rapidly and reflected the kinetic s of C3-fragment incorporation into the IC. Among eight donors, expres sing 180-361 CRI per E, >90% of the cell-bound IC were associated with E from 1 to 5 min of incubation, decreasing to 12 +/- 13% after 40 mi n. Upon comparison of the IC-binding to leucocytes in whole blood with that of isolated leucocytes we found that E, despite their extensive early complex uptake, only reduced the IC-deposition on polymorphonucl ear leucocytes (PMN) by 61 +/- 26% after 30 seconds of incubation and 47 +/- 14% after 5 min,During the subsequent 10 min, this buffering ca pacity of E was essentially abolished. E restricted the initial IC-bin ding to B cells by 73 +/- 19%, but from 3 min of incubation the presen ce of E promoted, in a CR1-dependent manner, a progressive uptake via CR2 by the B cells. CR1 was the dominant receptor in the early IC-upta ke by B cells as well as PMN and monocytes, since CR1-blockade inhibit ed the initial IC-uptake by these populations in a preparation of isol ated leucocytes suspended in serum by greater than or equal to 84% aft er 30 seconds of incubation. We conclude, that E exert a substantial b uffering effect on the IC-deposition on PMN, monocytes and B cells, wh ile CR1 is the dominant receptor in the uptake by these cells. However , this effect is short-lived and less than expected from the proportio n of IC bound to E. Moreover, E are efficient processors of IC-attache d C3b/iC3b fragments to C3dg as indicated by a pronounced enhancement by E of IC-uptake via CR2 on B cells. We propose that this mechanism m ay play a role in preventing phagocyte activation via CR3.