Both resting and activated B lymphocytes expressing engineered peptide- Ig molecules serve as highly efficient tolerogenic vehicles in immunocompetent adult recipients

• Published in: The Journal of immunology (1950) Vol. 158; no. 5; pp. 2174 - 2182
• Main Authors: Zambidis, ET, Barth, RK, Scott, DW
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 01.03.1997
• Subjects: Age Factors; Amino Acid Sequence; Animals; Antigen-Presenting Cells - immunology; B-Lymphocytes - cytology; B-Lymphocytes - immunology; B-Lymphocytes - metabolism; Bone Marrow - radiation effects; Epitopes - analysis; Female; Immune Tolerance; Immunity, Cellular - genetics; Immunization; Immunoglobulin G - administration & dosage; Immunoglobulin G - biosynthesis; Immunoglobulin G - genetics; Interphase - immunology; Lymphocyte Activation; Lymphoid Tissue - transplantation; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Transgenic; Molecular Sequence Data; Peptide Fragments - biosynthesis; Peptide Fragments - genetics; Peptide Fragments - immunology; Protein Engineering; Radiation Chimera; Recombinant Fusion Proteins - biosynthesis
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.158.5.2174

To test the potential for genetically transferring foreign sequences into autologous cells for specific modulation of immunity, we have generated transgenic mice that express an engineered peptide-IgG construct in the peripheral B cell compartment. B cells from these mice express and can be stimulated to secrete a murine IgG1 chain grafted with residues 12-26 from bacteriophage A cI repressor protein in-frame at the heavy chain N terminus. As expected, 12-26-IgG transgenic mice are profoundly tolerant to the peptide at both the T and B cell levels. Importantly, the injection of transgenic whole spleen, purified B cells, or even bone marrow cells into normal, immunocompetent adults results in profound peptide-specific T cell tolerance, as well as partial B cell tolerance. Injection of LPS-activated peptide-Ig-expressing B cells was uniquely effective at diminishing an ongoing humoral immune response typical of both Th1 and Th2 help. Since fixed transgenic B cells were tolerogenic, this suggests that secretion of the fusion protein is not required for tolerogenicity. These results show that an engineered self Ig, as well as B lymphocytes expressing epitopes from such a fusion protein, can regulate both cellular and humoral immune responses. Moreover, these studies provide the basis for expressing foreign epitopes on engineered IgG for the induction of gene-transferred tolerogenesis in autoimmune states.