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 Rewiring of B cell receptor signaling by Epstein–Barr virus LMP2A

2020 ◽  
Vol 117 (42) ◽  
pp. 26318-26327
Author(s):  
Kamonwan Fish ◽  
Federico Comoglio ◽  
Arthur L. Shaffer ◽  
Yanlong Ji ◽  
Kuan-Ting Pan ◽  
...  
Keyword(s):  
Cell Cycle ◽  
B Cells ◽  
B Cell ◽  
Epstein Barr Virus ◽  
Cell Receptor ◽  
B Cell Receptor ◽  
Barr Virus ◽  
Human B Cells ◽  
Bcr Signaling ◽  
Epstein Barr

Epstein–Barr virus (EBV) infects human B cells and reprograms them to allow virus replication and persistence. One key viral factor in this process is latent membrane protein 2A (LMP2A), which has been described as a B cell receptor (BCR) mimic promoting malignant transformation. However, how LMP2A signaling contributes to tumorigenesis remains elusive. By comparing LMP2A and BCR signaling in primary human B cells using phosphoproteomics and transcriptome profiling, we identified molecular mechanisms through which LMP2A affects B cell biology. Consistent with the literature, we found that LMP2A mimics a subset of BCR signaling events, including tyrosine phosphorylation of the kinase SYK, the calcium initiation complex consisting of BLNK, BTK, and PLCγ2, and its downstream transcription factor NFAT. However, the majority of LMP2A-induced signaling events markedly differed from those induced by BCR stimulation. These included differential phosphorylation of kinases, phosphatases, adaptor proteins, transcription factors such as nuclear factor κB (NF-κB) and TCF3, as well as widespread changes in the transcriptional output of LMP2A-expressing B cells. LMP2A affected apoptosis and cell-cycle checkpoints by dysregulating the expression of apoptosis regulators such as BCl-xL and the tumor suppressor retinoblastoma-associated protein 1 (RB1). LMP2A cooperated with MYC and mutant cyclin D3, two oncogenic drivers of Burkitt lymphoma, to promote proliferation and survival of primary human B cells by counteracting MYC-induced apoptosis and by inhibiting RB1 function, thereby promoting cell-cycle progression. Our results indicate that LMP2A is not a pure BCR mimic but rather rewires intracellular signaling in EBV-infected B cells that optimizes cell survival and proliferation, setting the stage for oncogenic transformation.

scholarly journals B-cell-activating factor inhibits CD20-mediated and B-cell receptor-mediated apoptosis in human B cells

Immunology ◽  
2008 ◽  
Vol 125 (4) ◽  
pp. 570-590 ◽  
Author(s):  
Yohei Saito ◽  
Yoshitaka Miyagawa ◽  
Keiko Onda ◽  
Hideki Nakajima ◽  
Ban Sato ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Cell Receptor ◽  
B Cell Receptor ◽  
B Cell Activating Factor ◽  
Human B Cells

Inhibition of B cell receptor-mediated activation of primary human B cells by coengagement of CD19 and FcγRIIb with Fc-engineered antibodies

2008 ◽  
Vol 45 (15) ◽  
pp. 3926-3933 ◽  
Author(s):  
Seung Y. Chu ◽  
Igor Vostiar ◽  
Sher Karki ◽  
Gregory L. Moore ◽  
Greg A. Lazar ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Cell Receptor ◽  
B Cell Receptor ◽  
Human B Cells
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