Human antilipid A monoclonal antibodies bind to human B cells and the i antigen on cord red blood cells.
We describe two independently derived human mAb, A6(H4C5) and 216, initially selected for their reactivity to the lipid A domain of bacterial LPS, which also react with the following Ag: the i Ag present on cord RBC, a ligand on human B lymphocytes, and to certain autoantigens, defining these mAb as polyreactive. Both mAb have specific affinity for a carbohydrate epitope consisting minimally of a disaccharide with an acyl substitution at the 2-carbon position. Structural examination of the diverse Ag recognized by the two antibodies reveals the presence of this carbohydrate structure required for antibody binding. A6(H4C5) and 216 are IgM in isotype, but differ in their L chain expression. Molecular analysis shows that both the mAb are encoded by a highly conserved VH4 gene, designated VH4-21. This gene encodes a number of autoantibodies, particularly cold agglutinins. Specific recognition of lipid A and of a carbohydrate epitope on B lymphocytes by the two human mAb suggests a dual function for the highly conserved VH4-21 gene in antibacterial response and in B cell development and regulation.
Bhat
N M
NM
Department of Gynecology and Obstetrics, Stanford Medical Center, CA 94305.
Bieber
M M
MM
Chapman
C J
CJ
Stevenson
F K
FK
Teng
N N
NN
D000373:Agglutinins / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D001483:Base Sequence; D003450:Cryoglobulins; D000939:Epitopes / Q000032:analysis; D005312:Fetal Blood / Q000276:immunology; D006801:Humans; D007048:I Blood-Group System / Q000276:immunology*; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D008050:Lipid A / Q000276:immunology*; D008969:Molecular Sequence Data
D000373:Agglutinins; D000911:Antibodies, Monoclonal; D001324:Autoantigens; D003450:Cryoglobulins; D000939:Epitopes; D007048:I Blood-Group System; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D008050:Lipid A; C029443:cold agglutinins