COEXPRESSION OF B7-1 AND ANTIGEN BLOCKS TOLERANCE INDUCTION TO ANTIGEN PRESENTED BY RESTING B-CELLS

To investigate a role for B cells as tolerogenic APCs in peripheral ly mphoid organs, we have developed a system in which B cells from mice t ransgenic for the membrane-bound form of human mu-chain are transferre d into nontransgenic recipients. Mice injected with B cells expressing human mu-chain became profoundly tolerant to human mu-chain, as shown by greatly reduced Ab responses following challenge with human mu-cha in in adjuvant. Adoptive transfer experiments showed that the recipien t's Th cell response to human mu-chain was impaired, When the human mu transgenic spleen cells were activated with LPS before transfer, they no longer induced tolerance. Spleen cells from double-transgenic mice expressing both human mu-chain and the costimulatory molecule B7-1 (C D80) also failed to induce tolerance to human mu-chain. However, neith er human mu transgenic LPS blasts nor double-transgenic B cells induce d an Ab response or primed for a secondary Ab response to Ag in adjuva nt. Therefore, we find that expression of B7-1 together with Ag can in terfere with tolerance induction without inducing Ab formation or prim ing for a secondary Ab response.