Regulation of anti-phosphatidylserine antibodies.
The degree of heavy chain (H) editing, the types of Vkappa editors, and the pattern of Jkappa usage are correlated with a range of the affinity of anti-DNA. This range was determined by the number and location of arginine (R) residues in the VH. We, here, changed a key arginine residue in the VH of anti-DNA transgene to glycine, which sharply reduces the affinity for dsDNA. However, complete reversion of this anti-DNA to germline enhances the affinity for phosphatidylserine (PS). The B cells of this low-affinity anti-DNA and anti-PS transgenic mouse are tightly regulated by receptor editing. Thus, anti-PS B cells are another example of a constitutive self-antigen regulated in the bone marrow.
Li
Hui
H
Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
Jiang
Yufei
Y
Cao
Hong
H
Radic
Marko
M
Prak
Eline Luning
EL
Weigert
Martin
M
D000818:Animals; D020296:Animals, Congenic; D017152:Antibodies, Antiphospholipid / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D001324:Autoantigens; D004247:DNA / Q000378:metabolism; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D015328:Gene Rearrangement, B-Lymphocyte, Light Chain; D006825:Hybridomas / Q000276:immunology; D007143:Immunoglobulin Heavy Chains / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D007145:Immunoglobulin kappa-Chains / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D010718:Phosphatidylserines / Q000276:immunology*; D017393:RNA Editing; D017634:Self Tolerance; D055672:Static Electricity
D017152:Antibodies, Antiphospholipid; D001324:Autoantigens; D007143:Immunoglobulin Heavy Chains; D007145:Immunoglobulin kappa-Chains; D010718:Phosphatidylserines; D004247:DNA