FHR3 Blocks C3d-Mediated Coactivation of Human B Cells.
Denise BuhlmannHannes U EberhardtAnna MedyukhinaWolfgang M ProdingerMarc Thilo FiggePeter F ZipfelChristine SkerkaPublished in: Journal of immunology (Baltimore, Md. : 1950) (2016)
The autoimmune renal disease deficient for complement factor H-related (CFHR) genes and autoantibody-positive form of hemolytic uremic syndrome is characterized by the presence of autoantibodies specific for the central complement regulator, factor H, combined with a homozygous deficiency, mostly in CFHR3 and CFHR1 Because FHR3 and FHR1 bind to C3d and inactivated C3b, which are ligands for complement receptor type 2 (CR2/CD21), the aim of the current study was to examine whether FHR3-C3d or FHR1-C3d complexes modulate B cell activation. Laser-scanning microscopy and automated image-based analysis showed that FHR3, but not FHR1 or factor H, blocked B cell activation by the BCR coreceptor complex (CD19/CD21/CD81). FHR3 bound to C3d, thereby inhibiting the interaction between C3d and CD21 and preventing colocalization of the coreceptor complex with the BCR. FHR3 neutralized the adjuvant effect of C3d on B cells, as shown by inhibited intracellular CD19 and Akt phosphorylation in Raji cells, as well as Ca(2+) release in peripheral B cells. In cases of CFHR3/CFHR1 deficiency, the FHR3 binding sites on C3d are occupied by factor H, which lacks B cell-inhibitory functions. These data provide evidence that FHR3, which is absent in patients with the autoimmune form of hemolytic uremic syndrome, is involved in B cell regulation.
Keyphrases
- acute lymphoblastic leukemia
- deep learning
- signaling pathway
- multiple sclerosis
- high throughput
- endothelial cells
- induced apoptosis
- systemic lupus erythematosus
- transcription factor
- tyrosine kinase
- early stage
- high resolution
- cell proliferation
- dna methylation
- nk cells
- drug induced
- high speed
- cell death
- single cell
- genome wide
- cell cycle arrest
- protein kinase
- optical coherence tomography
- big data
- pluripotent stem cells