The role of complement receptor type 1 (CR1, 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 which they bind opsonized immune complexes (IC) in competition with leucocytes expressing higher numbers of CR1 as well as other complement- and Fc-receptors. This may prevent inappropriate activation of phagocytic cells. We examined the distribution on whole blood cells of preformed tetanus toxoid (TT)/human anti-TT IC, opsonized in situ in 80% autologous serum. Binding to E occurred rapidly and reflected the kinetics of C3-fragment incorporation into the IC. Among eight donors, expressing 180-361 CR1 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 min. 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 polymorphonuclear leucocytes (PMN) by 61 +/- 26% after 30 seconds of incubation and 47 +/- 14% after 5 min. During the subsequent 10 min, this buffering capacity of E was essentially abolished E restricted the initial IC-binding to B cells by 73 +/- 19%, but from 3 min of incubation the presence 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-uptake by B cells as well as PMN and monocytes, since CR1-blockade inhibited the initial IC-uptake by these populations in a preparation of isolated leucocytes suspended in serum by > or = 84% after 30 seconds of incubation. We conclude, that E exert a substantial buffering effect on the IC-deposition on PMN, monocytes and B cells, while CR1 is the dominant receptor in the uptake by these cells. However, this effect is short-lived and less than expected from the proportion of IC bound to E. Moreover, E are efficient processors of IC-attached 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 may play a role in preventing phagocyte activation via CR3.
Nielsen
C H
CH
Department of Medical Microbiology, Odense University, Denmark.
Matthiesen
S H
SH
Lyng
I
I
Leslie
R G
RG
D000328:Adult; D000936:Antigen-Antibody Complex / Q000276:immunology* / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology; D018929:Cell Culture Techniques; D004912:Erythrocytes / Q000276:immunology*; D005260:Female; D006801:Humans; D008297:Male; D009000:Monocytes / Q000276:immunology; D009504:Neutrophils / Q000276:immunology; D010587:Phagocytosis / Q000276:immunology*; D017463:Receptors, Complement 3b / Q000276:immunology*; D013745:Tetanus Toxoid / Q000276:immunology
D000936:Antigen-Antibody Complex; D017463:Receptors, Complement 3b; D013745:Tetanus Toxoid