Comparative Effects of Human Igα and Igβ 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.