Comparative effects of human Ig alpha and Ig beta in inducing autoreactive antibodies against B cells in mice.
Human and mouse Ig alpha molecules share only 58% amino acid sequence identity in their extracellular regions. However, mice immunized with a recombinant Fc fusion protein containing the extracellular portion of human Ig alpha produced significant amounts of IgG capable of binding to Ig alpha on mouse B cells. The induced auto/cross-reactive Abs could down-regulate B cell levels and the consequent humoral immune responses against an irrelevant Ag in treated mice. Analogous immunization with an Fc fusion protein containing the extracellular portion of human Ig beta gave a much weaker response to mouse Ig beta, although human and mouse Ig beta, like their Ig alpha counterparts, share 56% sequence identity in their extracellular regions. Protein sequence analyses indicated that a potential immunogenic segment, located at the C-terminal loop of the extracellular domain, has an amino acid sequence that is identical between human and mouse Ig alpha. A mAb A01, which could bind to both human and mouse Ig alpha, was found to be specific to a peptide encompassing this immunogenic segment. These findings suggest that specific auto/cross-reactivity against self Ig alpha can be induced by a molecular mimicry presented by a foreign Ig alpha.
Sheu
Jim J C
JJ
Department of Life Science, National Tsing Hua University, Hsinchu, Taiwan.
Cheng
Tammy
T
Chen
Huan Y
HY
Lim
Carmay
C
Chang
Tse-Wen
TW
D000595:Amino Acid Sequence; D000818:Animals; D018033:Antibodies, Bispecific / Q000378:metabolism; D000937:Antigen-Antibody Reactions; D015703:Antigens, CD / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D001323:Autoantibodies / Q000096:biosynthesis* / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D001666:Binding Sites, Antibody; D051925:CD79 Antigens; D016923:Cell Death / Q000276:immunology; D002460:Cell Line; D015536:Down-Regulation / Q000276:immunology; D006801:Humans; D007106:Immune Sera / Q000378:metabolism; D007114:Immunization; D007141:Immunoglobulin Fc Fragments / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D007274:Injections, Intraperitoneal; D008231:Lymphopenia / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D011947:Receptors, Antigen, B-Cell / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000276:immunology
D018033:Antibodies, Bispecific; D015703:Antigens, CD; D001323:Autoantibodies; D051925:CD79 Antigens; C497881:CD79A protein, human; C497883:CD79B protein, human; C497882:Cd79a protein, mouse; C497884:Cd79b protein, mouse; D007106:Immune Sera; D007141:Immunoglobulin Fc Fragments; D011947:Receptors, Antigen, B-Cell; D011993:Recombinant Fusion Proteins; D010047:Ovalbumin