scholarly journals Coligation of the B Cell Receptor with Complement Receptor Type 2 (CR2/CD21) Using Its Natural Ligand C3dg: Activation without Engagement of an Inhibitory Signaling Pathway

2005 ◽  
Vol 174 (6) ◽  
pp. 3264-3272 ◽  
Author(s):  
Taras Lyubchenko ◽  
Joe Dal Porto ◽  
John C. Cambier ◽  
V. Michael Holers
Keyword(s):  
B Cell ◽  
Signaling Pathway ◽  
Cell Receptor ◽  
B Cell Receptor ◽  
Receptor Type ◽  
Complement Receptor ◽  
Complement Receptor Type ◽  
Natural Ligand ◽  
Inhibitory Signaling

scholarly journals Revisiting the Coreceptor Function of Complement Receptor Type 2 (CR2, CD21); Coengagement With the B-Cell Receptor Inhibits the Activation, Proliferation, and Antibody Production of Human B Cells

2021 ◽  
Vol 12 ◽  
Author(s):  
Kristóf G. Kovács ◽  
Bernadett Mácsik-Valent ◽  
János Matkó ◽  
Zsuzsa Bajtay ◽  
Anna Erdei
Keyword(s):  
B Cells ◽  
B Cell ◽  
Antibody Production ◽  
Cell Receptor ◽  
B Cell Receptor ◽  
Receptor Type ◽  
Complement Receptor ◽  
Complement Receptor Type ◽  
Human B Cells

The positive coreceptor function of complement receptor type 2 [CR2 (CD21)] on B cells is generally accepted, although its role in the enhancement of antibody production had only been proven in mice. The importance of this phenomenon prompted reinvestigation of the functional consequences of coclustering CD21 and the B cell receptor (BCR) on primary human cells. We found that, at non-stimulatory concentrations of anti-IgG/A/M, coclustering the BCR and CR2 enhanced the Ca2+ response, while activation marker expression, cytokine production, proliferation, and antibody production were all inhibited upon the coengagement of CR2 and BCR on human B cells. Thus, the “textbook dogma” claiming that C3d acts as an adjuvant to enhance humoral immunity is relevant only to mice and not to humans.

scholarly journals Mapping of the Epstein-Barr virus and C3dg binding sites to a common domain on complement receptor type 2.

1989 ◽  
Vol 170 (6) ◽  
pp. 1931-1946 ◽  
Author(s):  
C A Lowell ◽  
L B Klickstein ◽  
R H Carter ◽  
J A Mitchell ◽  
D T Fearon ◽  
...  
Keyword(s):  
B Cell ◽  
Epstein Barr Virus ◽  
Cell Receptor ◽  
Receptor Type ◽  
Complement Receptor ◽  
Complement Receptor Type ◽  
Barr Virus ◽  
Natural Ligand ◽  
Epstein Barr

Complement receptor type 2 (CR2;CD21), a member of the superfamily of proteins containing short consensus repeats (SCRs), is the B cell receptor for both the gp350/220 envelope protein of Epstein-Barr virus (EBV), and for the C3dg protein of complement. By analysis of CR2 deletion mutants and chimeras formed with CR1 (CD35) we determined that of the 15 SCRs in CR2, the NH2-terminal two SCRs are necessary and sufficient to bind both gp350/220 and C3dg with affinities equivalent to those of the wild-type receptor. The epitope for OKB-7, a mAb that blocks binding of both EBV and C3dg and shares with these ligands B cell-activating capabilities, also requires both SCR-1 and SCR-2, whereas mAbs lacking these functions bind to other SCRs. Thus, EBV, a polyclonal activator of B cells, has selected a site that is proximate or identical to the natural ligand binding site in CR2, perhaps reflecting the relative immutability of that site as well as its signal transducing function.

scholarly journals Analysis of C3-receptor activity on human B-lymphocytes and isolation of the complement receptor type 2 (CR2)

1984 ◽  
Vol 224 (1) ◽  
pp. 75-86 ◽  
Author(s):  
K J Micklem ◽  
R B Sim ◽  
E Sim
Keyword(s):  
Monoclonal Antibody ◽  
Affinity Chromatography ◽  
B Cell ◽  
B Lymphocytes ◽  
Receptor Type ◽  
Complement Receptor ◽  
Complement Receptor Type ◽  
Pure Protein

The rosetting of defined C3-fragment-coated sheep erythrocytes to B-cell-enriched tonsil lymphocytes was measured. The rosetting lymphocytes were homogeneous with respect to expression of C3b, iC3b and C3d receptors. Isolation of receptors for C3 fragments from surface-radioiodinated lymphocytes by affinity chromatography on immobilized C3u, iC3b and C3d,g produced two proteins with partially overlapping specificities. A protein of 240 000 Mr, recognized by the monoclonal antibody To5 and identified as CR1 (complement receptor type 1), had affinity for C3u and iC3b. A protein of 145 000 Mr, recognized by the monoclonal antibody B2, had affinity for all three C3 fragments. Inhibition of rosetting by antibodies to these proteins indicates that CR1 is responsible for C3b-mediated rosetting and that the 145000-Mr receptor (CR2) is responsible for C3d-mediated rosetting. Partial inhibition by both anti-CR1 and anti-CR2 antibodies of iC3b-mediated rosetting indicates that both receptors are involved in iC3b-mediated rosetting. No other protein appears to be involved in tonsil B-cell rosetting to C3-fragment-coated cells. A method for preparing CR2 from tonsil lymphocytes based on affinity chromatography on C3d,g-Sepharose has been developed. Forty tonsil pairs (2 × 10(10) B-cells) yield about 40 micrograms of pure protein equivalent to a purification of 6500-fold from a detergent extract.

Complement Receptor Type 2 Mediates Infection of the Human CD4-Negative Raji B-Cell Line with Opsonized HIV

1992 ◽  
Vol 36 (6) ◽  
pp. 879-883 ◽  
Author(s):  
V. BOYER ◽  
C. DELIBRIAS ◽  
N. NORAZ ◽  
E. FISCHER ◽  
M. D. KAZATCHKINE ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Line ◽  
Receptor Type ◽  
Complement Receptor ◽  
Complement Receptor Type

scholarly journals Complement Receptor Type 1 Suppresses Human B Cell Functions in SLE Patients

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Mariann Kremlitzka ◽  
Bernadett Mácsik-Valent ◽  
Anna Polgár ◽  
Emese Kiss ◽  
Gyula Poór ◽  
...  
Keyword(s):  
B Cell ◽  
B Lymphocytes ◽  
Cell Activation ◽  
Receptor Type ◽  
Complement Receptor ◽  
B Cell Activation ◽  
Complement Receptor Type ◽  
Cell Functions ◽  
Inhibitory Capacity

Complement receptors (CRs) play an integral role in innate immunity and also function to initiate and shape the adaptive immune response. Our earlier results showed that complement receptor type 1 (CR1, CD35) is a potent inhibitor of the B cell receptor- (BCR-) induced functions of human B lymphocytes. Here we show that this inhibition occurs already at the initial steps of B cell activation since ligation of CR1 reduces the BCR-induced phosphorylation of key signaling molecules such as Syk and mitogen activated protein kinases (MAPKs). Furthermore, our data give evidence that although B lymphocytes of active systemic lupus erythematosus (SLE) patients express lower level of CR1, the inhibitory capacity of this complement receptor is still maintained and its ligand-induced clustering results in significant inhibition of the main B cell functions, similar to that found in the case of healthy individuals. Since we have found that reduced CR1 expression of SLE patients does not affect the inhibitory capacity of the receptor, our results further support the therapeutical potential of CD35 targeting the decrease of B cell activation and autoantibody production in autoimmune patients.

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