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.
C3dg is a cleavage product of the C3 component of complement that can facilitate the coligation of the complement receptor 2 (CR2/CD21) with the BCR via C3dg/Ag complexes. This interaction can greatly amplify BCR-mediated signaling events and acts to lower the threshold for B cell activation. Although previous studies have used anti-CR2 Abs or used chimeric Ags in the context of BCR transgenic mice as surrogate C3d-containing ligands, we have used a physiological form of C3d to study signaling in B cells from wild-type C57BL/6 mice. We find that while CR2-enhanced BCR signaling causes intracellular Ca2+ mobilization and total pTyr phosphorylation of an intensity comparable to optimal BCR ligation using anti-IgM Abs, it does so with limited activation of inhibitory effectors (such as CD22, Src homology region 2 domain containing phosphatase 1, and SHIP-1) and without substantial receptor cross-linking. In summary, we demonstrate that CR2-enhanced BCR signaling may proceed not only through the previously described amplification of positive signaling pathways, but is potentially augmented by a lack of normal inhibitory/feedback signaling.
Lyubchenko
Taras
T
Department of Medicine, University of Colorado Health Sciences Center, Denver, CO 80220, USA. Taras.Lyubchenko@UCHSC.edu
dal Porto
Joe
J
Cambier
John C
JC
Holers
V Michael
VM
D000818:Animals; D018941:Antigens, CD19 / Q000235:genetics / Q000378:metabolism; D016175:B-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D020013:Calcium Signaling; D003179:Complement C3b / Q000378:metabolism*; D066298:In Vitro Techniques; D008024:Ligands; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010446:Peptide Fragments / Q000378:metabolism*; D010766:Phosphorylation; D011940:Receptor Aggregation; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D017464:Receptors, Complement 3d / Q000378:metabolism*; D015398:Signal Transduction
D018941:Antigens, CD19; D008024:Ligands; D010446:Peptide Fragments; D011947:Receptors, Antigen, B-Cell; D017464:Receptors, Complement 3d; C045477:complement C3d,g; D003179:Complement C3b