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Comparative Effects of Human Ig and Ig in Inducing Autoreactive Antibodies Against B Cells in Mice ¹

Jim J. C. Sheu^*, Tammy Cheng, Huan Y. Chen^*, Carmay Lim^, and Tse-Wen Chang^2,*,

Departments of ^* Life Science and Chemistry, National Tsing Hua University, Hsinchu, Taiwan; Institute of Biomedical Science, Academia Sinica, Taipei, Taiwan; and Development Center for Biotechnology, Taipei, Taiwan

Human and mouse Ig 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 produced significant amounts of IgG capable of binding to Ig 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 gave a much weaker response to mouse Ig, although human and mouse Ig, like their Ig 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. A mAb A01, which could bind to both human and mouse Ig, was found to be specific to a peptide encompassing this immunogenic segment. These findings suggest that specific auto/cross-reactivity against self Ig can be induced by a molecular mimicry presented by a foreign Ig.