The role of complement receptors type 1 (CR1, CD35) and 2 (CR2, CD21) in promoting C3 fragment deposition and membrane attack complex formation on normal peripheral human B cells

Claus Henrik Nielsen, Morten Løbner Pedersen, Hanne Vibeke Hansen Marquart, Wolfgang Maria Prodinger, Robert Graham Quinton Leslie

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

Normal human B lymphocytes are known to activate the alternative pathway (AP) of complement, leading to C3-fragment deposition and membrane attack complex (MAC) formation. The process is mediated via complement receptor type 2 (CR2, CD21), with complement receptor type 1 (CR1, CD35) playing a subsidiary role. In this study, we examine the relative contributions of CR1 and CR2 to the deposition of C3 fragments and MAC on B lymphocytes under circumstances where all complement pathways are operational. C3-fragment deposition and MAC formation were assessed on human peripheral B lymphocytes in the presence of 30% autologous serum. Blocking the CR2 ligand-binding site with monoclonal antibody (mAb) FE8 resulted in significant reduction (37.9+/-11.9%) in C3-fragment deposition, whereas MAC formation was only marginally affected (12.1+/-22.2% reduction). Blocking the CR1 binding-site resulted in significant reduction of both C3-fragment deposition (22.0+/-14.5%) and MAC formation (47.4+/-13.8%). Both the lack of CR2 influence on MAC formation and the promotion of C3-fragment deposition by CR1 are in striking contrast to the situation where only the AP is operational. The presence of erythrocytes (E) bearing CR1, however, markedly reduced both C3-fragment deposition and MAC formation. Our data suggest that C3-fragment deposition and MAC formation on B lymphocytes in vivo may involve both AP and classical pathway activation, with CR1 contributing significantly to the latter. On the other hand, the presence of extrinsic CR1, on E, may serve to limit spontaneous MAC formation and thereby ensure cell survival in the circulation.
OriginalsprogEngelsk
TidsskriftEuropean Journal of Immunology
Vol/bind32
Udgave nummer5
Sider (fra-til)1359-67
Antal sider9
ISSN0014-2980
StatusUdgivet - 2002

Fingeraftryk

Complement 3d Receptors
Complement Membrane Attack Complex
Complement Receptors
Alternative Complement Pathway
Cell Survival
Ligands

Citer dette

Nielsen, Claus Henrik ; Pedersen, Morten Løbner ; Marquart, Hanne Vibeke Hansen ; Prodinger, Wolfgang Maria ; Leslie, Robert Graham Quinton. / The role of complement receptors type 1 (CR1, CD35) and 2 (CR2, CD21) in promoting C3 fragment deposition and membrane attack complex formation on normal peripheral human B cells. I: European Journal of Immunology. 2002 ; Bind 32, Nr. 5. s. 1359-67.
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title = "The role of complement receptors type 1 (CR1, CD35) and 2 (CR2, CD21) in promoting C3 fragment deposition and membrane attack complex formation on normal peripheral human B cells",
abstract = "Normal human B lymphocytes are known to activate the alternative pathway (AP) of complement, leading to C3-fragment deposition and membrane attack complex (MAC) formation. The process is mediated via complement receptor type 2 (CR2, CD21), with complement receptor type 1 (CR1, CD35) playing a subsidiary role. In this study, we examine the relative contributions of CR1 and CR2 to the deposition of C3 fragments and MAC on B lymphocytes under circumstances where all complement pathways are operational. C3-fragment deposition and MAC formation were assessed on human peripheral B lymphocytes in the presence of 30{\%} autologous serum. Blocking the CR2 ligand-binding site with monoclonal antibody (mAb) FE8 resulted in significant reduction (37.9+/-11.9{\%}) in C3-fragment deposition, whereas MAC formation was only marginally affected (12.1+/-22.2{\%} reduction). Blocking the CR1 binding-site resulted in significant reduction of both C3-fragment deposition (22.0+/-14.5{\%}) and MAC formation (47.4+/-13.8{\%}). Both the lack of CR2 influence on MAC formation and the promotion of C3-fragment deposition by CR1 are in striking contrast to the situation where only the AP is operational. The presence of erythrocytes (E) bearing CR1, however, markedly reduced both C3-fragment deposition and MAC formation. Our data suggest that C3-fragment deposition and MAC formation on B lymphocytes in vivo may involve both AP and classical pathway activation, with CR1 contributing significantly to the latter. On the other hand, the presence of extrinsic CR1, on E, may serve to limit spontaneous MAC formation and thereby ensure cell survival in the circulation.",
keywords = "B-Lymphocytes, Cell Line, Cell Survival, Complement C1q, Complement C3, Complement Membrane Attack Complex, Complement Pathway, Alternative, Complement Pathway, Classical, Erythrocytes, Humans, Kinetics, Peptide Fragments, Receptors, Complement 3b, Receptors, Complement 3d",
author = "Nielsen, {Claus Henrik} and Pedersen, {Morten L{\o}bner} and Marquart, {Hanne Vibeke Hansen} and Prodinger, {Wolfgang Maria} and Leslie, {Robert Graham Quinton}",
year = "2002",
language = "English",
volume = "32",
pages = "1359--67",
journal = "European Journal of Immunology",
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The role of complement receptors type 1 (CR1, CD35) and 2 (CR2, CD21) in promoting C3 fragment deposition and membrane attack complex formation on normal peripheral human B cells. / Nielsen, Claus Henrik; Pedersen, Morten Løbner; Marquart, Hanne Vibeke Hansen; Prodinger, Wolfgang Maria; Leslie, Robert Graham Quinton.

I: European Journal of Immunology, Bind 32, Nr. 5, 2002, s. 1359-67.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - The role of complement receptors type 1 (CR1, CD35) and 2 (CR2, CD21) in promoting C3 fragment deposition and membrane attack complex formation on normal peripheral human B cells

AU - Nielsen, Claus Henrik

AU - Pedersen, Morten Løbner

AU - Marquart, Hanne Vibeke Hansen

AU - Prodinger, Wolfgang Maria

AU - Leslie, Robert Graham Quinton

PY - 2002

Y1 - 2002

N2 - Normal human B lymphocytes are known to activate the alternative pathway (AP) of complement, leading to C3-fragment deposition and membrane attack complex (MAC) formation. The process is mediated via complement receptor type 2 (CR2, CD21), with complement receptor type 1 (CR1, CD35) playing a subsidiary role. In this study, we examine the relative contributions of CR1 and CR2 to the deposition of C3 fragments and MAC on B lymphocytes under circumstances where all complement pathways are operational. C3-fragment deposition and MAC formation were assessed on human peripheral B lymphocytes in the presence of 30% autologous serum. Blocking the CR2 ligand-binding site with monoclonal antibody (mAb) FE8 resulted in significant reduction (37.9+/-11.9%) in C3-fragment deposition, whereas MAC formation was only marginally affected (12.1+/-22.2% reduction). Blocking the CR1 binding-site resulted in significant reduction of both C3-fragment deposition (22.0+/-14.5%) and MAC formation (47.4+/-13.8%). Both the lack of CR2 influence on MAC formation and the promotion of C3-fragment deposition by CR1 are in striking contrast to the situation where only the AP is operational. The presence of erythrocytes (E) bearing CR1, however, markedly reduced both C3-fragment deposition and MAC formation. Our data suggest that C3-fragment deposition and MAC formation on B lymphocytes in vivo may involve both AP and classical pathway activation, with CR1 contributing significantly to the latter. On the other hand, the presence of extrinsic CR1, on E, may serve to limit spontaneous MAC formation and thereby ensure cell survival in the circulation.

AB - Normal human B lymphocytes are known to activate the alternative pathway (AP) of complement, leading to C3-fragment deposition and membrane attack complex (MAC) formation. The process is mediated via complement receptor type 2 (CR2, CD21), with complement receptor type 1 (CR1, CD35) playing a subsidiary role. In this study, we examine the relative contributions of CR1 and CR2 to the deposition of C3 fragments and MAC on B lymphocytes under circumstances where all complement pathways are operational. C3-fragment deposition and MAC formation were assessed on human peripheral B lymphocytes in the presence of 30% autologous serum. Blocking the CR2 ligand-binding site with monoclonal antibody (mAb) FE8 resulted in significant reduction (37.9+/-11.9%) in C3-fragment deposition, whereas MAC formation was only marginally affected (12.1+/-22.2% reduction). Blocking the CR1 binding-site resulted in significant reduction of both C3-fragment deposition (22.0+/-14.5%) and MAC formation (47.4+/-13.8%). Both the lack of CR2 influence on MAC formation and the promotion of C3-fragment deposition by CR1 are in striking contrast to the situation where only the AP is operational. The presence of erythrocytes (E) bearing CR1, however, markedly reduced both C3-fragment deposition and MAC formation. Our data suggest that C3-fragment deposition and MAC formation on B lymphocytes in vivo may involve both AP and classical pathway activation, with CR1 contributing significantly to the latter. On the other hand, the presence of extrinsic CR1, on E, may serve to limit spontaneous MAC formation and thereby ensure cell survival in the circulation.

KW - B-Lymphocytes

KW - Cell Line

KW - Cell Survival

KW - Complement C1q

KW - Complement C3

KW - Complement Membrane Attack Complex

KW - Complement Pathway, Alternative

KW - Complement Pathway, Classical

KW - Erythrocytes

KW - Humans

KW - Kinetics

KW - Peptide Fragments

KW - Receptors, Complement 3b

KW - Receptors, Complement 3d

M3 - Journal article

VL - 32

SP - 1359

EP - 1367

JO - European Journal of Immunology

JF - European Journal of Immunology

SN - 0014-2980

IS - 5

ER -