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and Ig
in Inducing Autoreactive Antibodies Against B Cells in Mice 1

,

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
.
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