BOTH RESTING AND ACTIVATED B-LYMPHOCYTES EXPRESSING ENGINEERED PEPTIDE-IG MOLECULES SERVE AS HIGHLY EFFICIENT TOLEROGENIC VEHICLES IN IMMUNOCOMPETENT ADULT RECIPIENTS
Et. Zambidis et al., BOTH RESTING AND ACTIVATED B-LYMPHOCYTES EXPRESSING ENGINEERED PEPTIDE-IG MOLECULES SERVE AS HIGHLY EFFICIENT TOLEROGENIC VEHICLES IN IMMUNOCOMPETENT ADULT RECIPIENTS, The Journal of immunology, 158(5), 1997, pp. 2174-2182
To test the potential for genetically transferring foreign sequences i
nto autologous cells for specific modulation of immunity, we have gene
rated 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 res
idues 12-26 from bacteriophage lambda cl repressor protein in-frame at
the heavy chain N terminus. As expected, 12-26-IgG transgenic mice ar
e profoundly tolerant to the peptide at both the T and B cell levels.
Importantly, the injection of transgenic whole spleen, purified B cell
s, or even bone marrow cells into normal, immunocompetent adults resul
ts in profound peptide-specific T cell tolerance, as well as partial B
cell tolerance, Injection of LPS-activated peptide-Ig-expressing B ce
lls was uniquely effective at diminishing an ongoing humoral immune re
sponse typical of both Th1 and Th2 help. Since fixed transgenic B cell
s were tolerogenic, this suggests that secretion of the fusion protein
is not required for tolerogenicity. These results show that an engine
ered self Ig, as well as B lymphocytes expressing epitopes from such a
fusion protein, can regulate both cellular and humoral immune respons
es. Moreover, these studies provide the basis for expressing foreign e
pitopes on engineered IgG for the induction of gene-transferred tolero
genesis in autoimmune states.