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PubMed1976

Complement system in pneumococcal infections.

The properdin or alternate complement pathway may function as a heat-labile opsonin for pneumococci, and evidence has been sought for its activation in pneumococcal infections. Twenty-two patients had determinations of C1q, C4, properdin factor B, C3, and hemolytic complement during hospitalization for pneumococcal infection. Measurements were made during the first 36 h after admission on 16 patients and later during recovery on 16. The admission and recovery values were compared statistically with each other and with the levels of 15 normal individuals. The admission and recovery mean values were normal and nearly identical for C1q and C4, which are two early components of the classical pathway. The mean level of factor N, a properdin pathway component, was significantly depressed on admission, but the mean recovery value was normal. Admission levels for C3, a component of the late common pathway, were depressed, and recovery values were normal. Total hemolytic complement was decreased on admission, although the decrease was not significant for the patients with both admission and recovery determinations. The findings are consistent with the hypothesis that factor B is turned over rapidly, or consumed, early in pneumococcal infections; alternatively, persons with low baseline factor B levels may be particularly susceptible to pneumococcal infection.

Adult↗

PubMed1977

Complement levels in pneumococcal pneumonia.

Levels of complement proteins and functional activity of the alternate complement pathway were assessed in 39 patients with pneumococcal pneumonia. Mean levels of C3 and properdin and the functional activity of the alternate pathway in acute sera were significantly (P less than 0.05) below normal, whereas levels of components of the early classical pathway were normal. Although levels of factor B were in the normal range, they correlated significantly with C3 levels; there was no significant relation between C3 levels and C4 or C1q levels. The 19 patients iwth pneumococcal pneumonia and bacteremia had significantly lower mean values of properdin and factor B than the 20 patients without bacteremia, suggesting a more severe depression of the alternate complement pathway with bacteremia. During convalescence, complement levels were normal or elevated in most of the patients, but mean levels of properdin remained significantly below normal in bacteremic patients. Functional activity of the alternate pathway also remained below normal. These results indicate that there is a selective depression of the alternate pathway in patients with pneumococcal pneumonia, and they are consistent with the concept that the alternate pathway has an important role in host defenses in pneumococcal infection.

Adult↗

PubMed1975

Complement breakdown products in plasma from patients with systemic lupus erythematosus and patients with membranoproliferative or other glomerulonephritis.

A dynamic estimation of the involvement of the complement system in various diseases was obtained by the direct quantitation of breakdown products of C3 and of properdin factor B. The methods used were based, first on the separation of native and fragmented molecules according to their molecular size through a precipitation with polyethylene glycol and, secondly, on an immunochemical quantitation, using specific antisera for the major antigens of C3 and factor B. The sensitivity and the specificity of these methods were demonstrated by activation of complement in vitro with generation of C3 and factor B fragments. A clinical investigation was carried out in 41 patients with systemic lupus erythematosus (SLE), 31 with membranoproliferative glomerulonephritis (MPGN), 26 with other types of glomerulonephritis, and 6 with severe alcoholic cirrhosis of the liver. The following observations were made: (a) an elevated plasma level of C3d fragment of C3 was found in 68% of SLE patients, in 87% of MPGN patients, in 62% of patients with other hypocomplementemic nephritis, and in 15% of those with normocomplementemic nephritis, but in only 33% of patients with liver cirrhosis and very low levels of C3; (b) a significant difference was observed between the levels of C3 obtained with either anti-"native" C3 or anti-C3c sera for immunochemical quantitation, in patients with SLE or MPGN, indicating the presence of "altered" or fragmented C3 in plasma; (c) an elevated plasma level of Ba fragment of properdin factor B was found in 46% of SLE patients, in 67% of MPGN patients, in 50% of patients with other hypocomplementemic nephritis, and in 9% of patients with normocomplementemic nephritis, while the level of properdin factor B was only slightly decreased in these diseases; (d) in SLE and MPGN there was an inverse correlation between the levels of C3d and Ba and the level of C3 in plasma. The level of these fragments was directly correlated with the clinical manifestations of SLE; (e) some patients with a normal C3 level exhibited an elevated plasma concentration of C3 and factor B fragments, suggesting the coexistence of an increased synthesis with a hypercatabolism of complement components. Therefore, the quantitation of complement breakdown products by simple immunochemical methods provides additional information concerning the involvement of complement in disease and new features for the evaluation of the intensity of immune reactions during immune complex diseases.

Adolescent↗

PubMed2002

Immunological activity of larch arabinogalactan and Echinacea: a preliminary, randomized, double-blind, placebo-controlled trial.

UNLABELLED: The immunomodulating effects of two Echinacea species, E. purpurea and E. angustifolia and larch arabinogalactan extracted from Larix occidentalis were examined in a randomized, double-blind, placebo-controlled, prospective four-week clinical trial at a naturopathic medical school research center. SUBJECTS/MATERIALS: Forty-eight healthy female volunteers (22-51 y) were randomly assigned to one of six groups: standardized extract of E. purpurea (EP); ultra-refined E. purpurea/E. angustifolia (urEPA); E. purpurea/E. angustifolia (EPA); E. purpurea/E. angustifolia plus larch arabinogalactan (EPALA); larch arabinogalactan (LA); or placebo. METHODS: Immunological tests with enumerative measurements, stool cultures for Lactobacillus acidophilus and yeast, and health-related quality of life (HRQoL) using the Medical Outcomes Study derived SF-36 self-administered questionnaire were assessed at baseline and at four weeks. RESULTS: Complement properdin increased by 21 percent in the EPA group (p<0.05) and by 18 percent in the EPALA group (p<0.05), compared to the placebo group (p>0.05). SF-36 showed improvements in overall physical health, vitality, and emotional health in the same two groups (EPA and EPALA). DISCUSSION: Volunteers in the EPA and EPALA groups had increased production of complement properdin after four weeks of intervention. The increased complement properdin may be an indication of one aspect of immune system stimulation in patients treated with either E. purpurea/E. angustifolia or E. purpurea/E. angustifolia plus larch arabinogalactan.

Adult↗

PubMedDate not supplied

[Various non-specific immunity proteins in the blood serum of workers in the coke-processing industry].

The concentrations of certain proteins related to non-specific immunity were determined in the serum of cokery workers and in a matched control group. No changes were found in the concentrations of the main proteins of the properdin system, that is properdin and third fraction of complement. However, the level of transferrin was higher in cokery workers. It seems that the harmful effects of the working environment were not changing the function of the properdin system. Raised transferrin level seems to be only a biochemical trace of exposure without essential importance.

Adult↗

PubMed1978

[Nonspecific resistance in germ-free and E. coli monocontaminated miniature piglets].

Phagocytic activity of leukocytes, as well as the complement, properdin, and lysozyme levels in the blood serum of miniature piglets, germfree and monocontaminated with E. coli 055 and E. coli 083, were studied. E. coli 055 phagocytosis was decreased in the presence of autologous serum and complement and increased under the effect of specific opsonins (antibodies to E. coli 055). Complement, properdin, and lysozyme levels were decreased in the germfree, in comparison with conventional animals. In the E. coli contaminated piglets properdin and complement production was stimulated most, and lysozyme formation--less. No antibodies to E. coli 055 were revealed in monocontaminated piglets. The highest lysozyme levels were found in the ex-germfree animals, this indicating the participation of factors other than E. coli contamination in lysozyme stimulation. It is concluded that microbial contamination played an important role in the development of cellular and humoral factors of the organism resistance.

Animals↗

PubMed1979

Immunofluorescence studies of dense deposit disease. The presence of railroad tracks and mesangial rings.

Immunopathologic analysis was carried out on renal tissue from patients with membranoproliferative glomerulonephritis, nine with type I and nine with type II (dense deposit disease). A specific finding in all patients with type II, but not type I, was the presence of C3 along the margin but not within the central portion of dense deposit material in the glomerular basement membrane giving a double linear appearance (railroad tracks); C3 was also present within the mesangium, outlining numerous circular structures (mesangial rings). By phase contrast, electron microscopy, and dual label fluorescence studies, the railroad tracks and mesangial rings were shown to outline dense deposit material. Mesangial rings contained properdin (four of nine patients); railroad tracks contained properdin (five of nine patients) and C4 (four of nine patients); no other complement components or immunoglobulins were present. Studies using rhodamine-conjugated rabbit antibody to human glomerular basement membrane demonstrated no reactivity with the dense deposit material itself. In type I and to a lesser extent in type II, granular deposits of C3, C4, properdin, IgM, and IgG were present along the glomerular basement membrane, suggesting that immune complexes play a role in both diseases. Dense deposit transformation of the glomerular basement membrane may be a consequence of a highly specific injury.

Autoantibodies↗

PubMed1976

Immunopathology of the end-stage kidney. Immunoglobulin and complement component deposition in nonimmune disease.

Seventy nephrectomy specimens from patients with end-stage renal disease, four renal biopsies from patients with focal sclerosing glomerulonephropathy (FSGN) and normal renal function, and 17 control biopsies from normal renal allograft donors (Group I) were studied by immunofluorescence with respect to deposition of immunoglobulins and classic and alternative complement (C) pathway components. The end-stage kidneys were divided into three groups according to etiology: 16 patients with immune-mediated glomerulonephritis (Group II), 22 patients with congenital and/or familial renal disease (Group III), and 32 patients with systemic or primary renal disease in which an immune-mediated injury could not be established (Group IV). The pattern of immunoprotein deposition in glomeruli in Groups II, III, and IV, and in biopsies of patients with FSGN was similar: peripheral lobular, globular and/or granular, focal and segmental; it was limited to dying glomeruli or abnormal glomerular segments. A statistically significant correlation existed between the percent of properdin-containing glomeruli and the percent of glomeruli undergoing hyalinization in Groups II, III and IV (II, r=0.67; III, r=0.92; IV, r=0.78). No deposition was observed in normal or completely fibrotic glomeruli. In vitro heterologous complement fixation was demonstrated in 17/19 end-stage kidneys in a similar distribution. Early classic C components, C1q and C4, were detected in a somewhat higher frequency in Group II (14/16) than Group III (11/22) and Group IV (20/32) (Group II vs. III, P=.02 and II vs. IV, P=.07). C3 and properdin were detected in 77 to 100% of all 3 groups; in 18 patients, C3 and properdin were present without detectable C1q and C4. Immunoglobulins, primarily IgM, and components of the classic and alternative C pathways are regularly present in hyalinizing glomeruli irrespective of the etiology of the renal failure. These observations suggest that an immune process is operative in glomerular obsolescence regardless of the underlying etiology of the renal disease.

Adolescent↗

PubMed1994

The type 1 repeats of thrombospondin 1 activate latent transforming growth factor-beta.

Thrombospondin (TSP) is complexed with transforming growth factor-beta (TGF-beta) in the alpha-granules of stimulated platelets. TSP stripped of associated TGF-beta activity (sTSP) activates latent TGF-beta secreted by bovine aortic endothelial cells (BAE) in culture. To better understand the interactions of TSP with TGF-beta, we investigated which region of sTSP interacts with TGF-beta. The chymotrypsin-resistant core of TSP, which contains the procollagen-like region and the properdin-like type 1 repeats, activated both latent TGF-beta secreted by BAE and a recombinant form of the small latent TGF-beta complex at levels similar to or better than sTSP. The core fragment bound 125I-TGF-beta in solution and shifted the elution profile of 125I-TGF-beta in gel permeation chromatography. Fusion constructs of the type 1, 2, and 3 repeats and the COOH terminus of TSP1 were tested for their ability to activate latent TGF-beta. Only the type 1 construct, containing the three properdin-like repeats of TSP found in the 50-kDa fragment, activated latent TGF-beta. In addition, a polyclonal antibody against the type 1 construct inhibits activation of latent TGF-beta by intact TSP, suggesting that this region is exposed in the intact molecule. These results show that the type 1 properdin-like repeats of TSP are responsible for activating recombinant and endothelial cell-derived latent TGF-beta and that this site is exposed in intact TSP.

Amino Acid Sequence↗

PubMed1993

Herpes simplex virus glycoprotein C: molecular mimicry of complement regulatory proteins by a viral protein.

Herpes simplex virus (HSV) encodes a protein, glycoprotein C (gC), which binds to the third complement component, the central mediator of complement activation. In this study the structural and functional relationships of gC from HSV type 1 (HSV-1) and known human complement regulatory proteins factor H, properdin, factor B, complement receptor 1 (CR1) and 2 (CR2) were investigated. The interaction of gC with C3b was studied using purified complement components, synthetic peptides, antisera against different C3 fragments and anti-C3 monoclonal antibodies (mAb) with known inhibitory effects on C3-ligand interactions. All the mAb that inhibited gC/C3b interactions, in a differential manner, also prevented binding of C3 fragments to factors H, B, CR1 or CR2. No blocking was observed with synthetic peptides representing different C3 regions or with factor B and C3d, whereas C3b, C3c and factor H were inhibitory, as well as purified gC. There was no binding of gC to cobra venom factor (CVF), a C3c-like fragment derived from cobra gland. Purified gC bound to iC3, iC3b and C3c, but failed to bind to C3d. Glycoprotein C bound only weakly to iC3 derived from bovine and porcine plasma, thus indicating a preference of the viral protein for the appropriate host. Binding of gC was also observed to proteolytic C3 fragments, especially to the beta-chain, thus suggesting the importance of the C3 region as a binding site. Purified gC from HSV-1, but not HSV-2, inhibited the binding of factor H and properdin but not of CR1 to C3b. The binding of iC3b to CR2, a molecule involved in B-cell activation and binding of the Epstein-Barr virus, was also inhibited by the HSV-1 protein. As factor H and properdin, the binding of which was inhibited by gC, are important regulators of the alternative complement pathway, these data further support a role of gC in the evasion of HSV from a major first-line host defence mechanism, i.e. the complement system. In addition, the inhibition of the C3/CR2 interaction may suggest a possible immunoregulatory role of HSV glycoprotein C.

Antibodies, Monoclonal↗

PubMed1993

Expression of the components and regulatory proteins of the alternative complement pathway and the membrane attack complex in normal and diseased synovium.

We have studied synthesis of the complement components and regulatory proteins of the alternative pathway and the membrane attack complex in synovial membrane. RNA was extracted from synovial tissue of patients with rheumatoid arthritis (RA) or osteoarthritis (OA) as well as from normal synovial membrane. Dot blot analysis showed the presence of mRNAs for all the complement components and regulatory proteins (C3, factor B, factor D, C5, C6, C7, C9, factor H, factor I, S-protein, SP-40, 40, DAF, MCP, CR1, CD59), except for properdin, C8 alpha, C8 beta and C8 gamma in all three types of synovial membrane studied. In an attempt to determine which components were synthesised by each cell type, monocytes (mononuclear phagocytes), human umbilical vein endothelial cells (HUVEC), synovial membrane fibroblasts (from normal, OA and RA synovial membrane) and peripheral blood lymphocytes were cultured in vitro and secretion rates of individual components were measured and total cellular RNA analysed by northern blotting. Monocytes secreted properdin, C3, and factor H but not factor B, factor I, C5, C6, C7, C8 or C9. Fibroblasts and endothelial cells secreted factor B, factor H and factor I, but not properdin, C5, C6, C7, C8 or C9. Lymphocytes did not secrete any of these components. mRNAs encoding C3, factor B, factor H, S-protein, SP-40, 40, MCP and DAF were detected in all three other cell types (monocytes, fibroblasts and HU-VEC), but factor I and CD59 mRNAs were not detected in monocytes. C5, C6, C7, C8 alpha, C8 beta, CD8 gamma and C9 mRNAs were not detected in any of the cell types studied.(ABSTRACT TRUNCATED AT 250 WORDS)

Arthritis, Rheumatoid↗

PubMed1983

The C3/C5 convertase of the alternative pathway of complement: stabilization and restriction of control by lanthanide ions.

The alternative pathway C3 convertase (C3b,Bb) is a Mg-dependent, labile enzyme with a t/2 of 3 min at 37 degrees C and of 14 min at 24 degrees C (at half physiological ionic strength). To stabilize the enzyme, metal ions of the lanthanide series were tested. Formation and decay of the enzyme as well as binding of radiolabeled Factor B, Factor H or properdin to C3b were measured using C3b-bearing sheep erythrocytes (EC3b). Binding of Factor B to EC3b in presence of 40 microM gadolinium (Gd) was two to three times greater than in presence of 1 mM Mg. Binding of Factor H and of properdin to EC3b was partially inhibited by Gd. Although it enhanced Factor B uptake by EC3b, Gd was unable to substitute for Mg in enzyme formation by Factor D and completely inhibited (at 10 microM) Mg-dependent enzyme activation. However, the preformed enzyme was not inhibited by Gd. Instead, exposure of EC3b,Bb to 40-100 microM Gd increased the t/2 at 37 degrees C from 3 min to 12-28 min, and at 24 degrees C from 14 min to 32 min. The slow decay of the enzyme correlated with slow release of Bb. Similar enzyme stabilization was observed using terbium, ytterbium, dysprosium and lanthanum. The Gd stabilized enzyme was also less susceptible to control by Factor H and properdin than the unstabilized enzyme. Furthermore, Gd protected surface bound-C3b from being cleaved by Factor I. The Gd effects were instantaneously reversed upon addition of 10 mM EDTA. Thus, Gd is able to stabilize preformed C3b,Bb and to render the enzyme refractory to control by Factors H and I.

Cations, Divalent↗

PubMed1990

Patterns of complement activation in idiopathic membranoproliferative glomerulonephritis, types I, II, and III.

Complement profiles on 22 hypocomplementemic patients with membranoproliferative glomerulonephritis (MPGN) type I, on 11 with MPGN II, and on 16 with MPGN III, gave evidence that the nephritic factor of the amplification loop (NFa) is responsible for the hypocomplementemia in MPGN II and the nephritic factor of the terminal pathway (NFt) for the hypocomplementemia in MPGN III. In contrast, in MPGN I, there was evidence for three complement-activating modalities, NFa, NFt, and immune complexes. As a result, four different patterns of complement activation were seen. NFa, found in MPGN II, produces a complement profile characterized mainly by C3 depression. In addition, four of seven (57%) severely hypocomplementemic MPGN II patients (C3 less than 30 mg/dL) had slightly depressed levels of factor B, and one of seven (14%) of properdin, but in all the C5 concentration was normal. In contrast, all eight severely hypocomplementemic patients with MPGN II had depressed C5 and properdin levels, and six of eight (75%) depressed levels of C6, C7, and/or C9. Of eight MPGN III patients with moderate hypocomplementemia, 50% had depressed C5 and properdin levels and the remainder, depressed C3 only. This spectrum of profiles is most likely produced by varying concentrations of NFt. In MPGN I, nine of 23 (39%) had a profile indicating only classical pathway activation; seven of 23 (39%), a pattern compatible with NFt alone; four of 23 (9%), evidence for both classical pathway activation and NFt; and three of 23 (13%), a pattern compatible with NFa. The unique multifactorial origin of the hypocomplementemia in MPGN I, often giving evidence of classical pathway activation, together with previously reported differences in glomerular morphology and clinical features at onset, makes it distinct from MPGN III. Depressed C8 levels were found to some extent in all hypocomplementemic states. The levels were uncommonly depressed in patients with NFa, most markedly depressed with NFt, and moderately reduced with classical pathway activation. The cause is not known. Diagnostically, profiles showing classical pathway activation and low levels of C6, C7, and/or C9 are specific for MPGN I. Those showing only classical activation are likewise diagnostic of MPGN I if systemic lupus erythematosus (SLE) and chronic bacteremia are ruled out.

Complement Activation↗

PubMed1995

Interaction of several complement proteins with gp120 and gp41, the two envelope glycoproteins of HIV-1.

OBJECTIVE: To study the binding of human complement proteins to gp41 and gp120 of HIV-1. METHODS: The interaction of complement proteins with gp41 and gp120 and their effect on the gp41-gp120 complex in enzyme-linked immunosorbent assays (ELISA) and on stably transfected Schneider-2 cells expressing a gp41-gp120 complex was investigated. The molecular basis of these interactions was analysed by computer-supported sequence analysis. RESULT: gp41 strongly binds human complement regulatory proteins factors H and properdin, and weakly binds factors I and B. The binding occurs with recombinant soluble (rs) gp41 fixed on ELISA plates as well as gp41-gp120 complex expressed on Schneider-2 cells. The basis for this binding potential might be an amino-acid (aa) sequence of gp41 displaying homologies to sites in human C3. rgp120 also binds C3(H2O), a C3b-like form of C3, and C4b. These binding features of gp120 can be explained by homology of constant region (CR) 4 in gp120 to sites in C4b binding protein. Additionally, CR1 in gp120 exhibits a weak similarity to human properdin. Preincubation of rsgp41 with either factor H or properdin, and of rgp120 with C3b or C4b affected the interaction between rsgp41 and rgp120. Incubation of Schneider-2 cells, expressing a functional gp41-gp120 complex, with factor H reduced the detectable amount of gp120. This effect was similar to that induced by soluble CD4. CONCLUSION: These results strongly suggest that HIV-1 envelope proteins interact with human complement proteins. Additionally, C3b-like features of gp41 and the C3b/C4b binding structures in gp120 may affect the non-covalent association between gp41 and gp120.

Amino Acid Sequence↗

PubMed1979

Alternative pathway of complement activation in full term and premature infants.

Classical and alternative pathway complement levels were measured in the cord blood sera of 60 newly born infants, with weights ranging from 1200--4165 g. The impact of maternal illness and infant illness on the complement levels was also evaluated. The mean values for CH50, C3, C4, PH50, factor B, and properdin were all significantly less than normal adult levels (P less than 0.0001). All of the above determinations were significantly correlated with one another except for the relationship between properdin and factor B. CH50, PH50, C4, and properdin levels were significantly correlated with birth weight although there was much residual scatter. Neither maternal illness nor mild to moderate illness in the newborn altered the birth weight-complement relationships. Severe infant illness did significantly alter the relationship between birth weight and complement. However, the impact of this variable on the birth weight-complement relationships was not consistent among the various components. These inconsistencies and the small sample size preclude drawing any strong conclusions about severe illness and complement levels.

Adult↗

PubMedDate not supplied

[Complement and immunoglobulin levels in pregnant women with EPH gestosis].

The authors determined C3 and C4 complements, factor B properdin and immunoglobulins G, M and A in 20 healthy pregnant patients and in 20 patients with EPH gestosis. The analysis was performed in mothers sera, umbilical sera and amniotic fluid, and properdin factor B and IgG in urine. They used the nonfellometric technique with immunochemistry analyzer. The C3 complement was very increased in the serum of mothers with EPH gestosis, and complement C4 was slightly increased in the serum of EPH gestosis, and complement C4 was slightly in the serum of EPH gestosis, and complement C4 was slightly increased in the serum of mothers and umbilical sera. Factor B properdin was very increased in mothers sera and decreased in urine. Higher concentrations of immunoglobulin G were found in umbilical sera than in mothers sera. Increased concentrations of sera in mothers, the umbilicus and urine were observed in patients with EPH gestosis. In these patients IgM was decreased in the serum of mothers and the umbilicus. IgM was decreased in the serum of mothers and significantly increased in umbilical sera. Significant changes in patients with EPH gestosis were noted.

Complement Factor B↗

PubMed1980

[Significance of immunocomplexes and complement in renal transplantation. Preliminary data].

The authors have measured circulating immune complexes (ic) and some components (C1q, C4, C3 and properdin factor B) in 87 serum samples obtained during the follow-up of five renal transplantation. Results showed high serum levels of ic with normal renal function of the graft especially in one patient, and an increase of the values in some rejection crises. The behaviour of the complement system was variable for the different components, while frequently low properdin factor B serum levels were noticed in some renal transplantations during the normal function of the graft and during the rejection crisis. In conclusion, the Authors report that a) high levels of ic can be seen also in grafts with normal function and their presence may be correlated with viral infections; b) an increase of ic during the rejection crisis is due to humoral immune response; c) the reduction of C3 and C1q associated to an increase of ic has been frequently seen, and finally; d) the low levels of properdin factor B show a probable intervention of the alternative complement pathway in the rejection crisis.

Antigen-Antibody Complex↗

PubMed1997

A novel mechanism of alternative pathway complement activation accounts for the deposition of C3 fragments on CR2-expressing homologous cells.

Complement receptor type 2 (CD21, CR2), the receptor for the C3 fragment C3dg, activates complement via the alternative pathway and also serves as a preferential acceptor site for C3 fragments. The molecular basis for this phenomenon, which has recently been demonstrated for B lymphocytes in vivo, is currently not understood. Here we present a model for this CR2-dependent complement activation. The inactive C3 (iC3), which forms spontaneously in serum in low amounts by reaction of native C3 with H2O, binds noncovalently to the N-terminal part of CR2. Subsequent association of properdin and factor B, and cleavage of factor B by factor D lead to formation of a C3 convertase associated with CR2, thus focussing covalent C3 deposition to CR2 itself. This model is supported by the following experimental findings. 1) By FACS analysis and radioreceptor assays we showed that iC3, properdin, and factor B bound to CR2 on Raji B cells, MT2 T cells, and peripheral blood B cells. 2) Both binding of these proteins and complement activation by CR2-expressing cells were reduced in parallel by Abs against CR2. 3) 125I-labeled C3b was covalently deposited on CR2, when hemolytically active 125I-labeled C3 was added to Raji cells preincubated with iC3, factor B, properdin, and factor D, thus proving functionality of CR2-bound C3 convertase. This model of C3 convertase activity formed on CR2 domains inaccessible for decay-accelerating factor offers an explanation for the deposition of C3 found on CR2-expressing cells.

B-Lymphocytes↗