Tolerance induction with an engineered peptide-IgG fusion protein using retrovirally infected bone marrow cells

A murine IgG₁ H chain has been "grafted" in frame at the N-terminus with residues 12-26 of bacteriophage λ cI represser, which contains an immunodominant T-cell and B-cell epitope. Using a retroviral vector for expression of this engineered self-Ig construct, we have shown that recipients of transduced marrow-derived cells are specifically tolerant to 12-26 in terms of cytokine production and T-cell help, whereas they respond normally to hen lysozyme. To test whether antigen presentation by B cells was responsible for the tolerogenic effects, we transferred B cells from transgenic mice expressing this engineered Ig and observed that both small, resting B cells and LPS blasts were tolerogenic for 12-26 even in non-irradiated recipients. Since BM cells from SCID donors can also be transduced to produce tolerogenic APC and the degree of unresponsiveness in recipients does not correlate with the level of serum expression of the engineered IgG, we suggest that non-B cells can also present the engineered peptide in a tolerogenic manner. These data suggest that several types of APC may be functionally tolerogenic in naive recipients. We are currently investigating whether this system can be rendered effective in primed animals.