B7 COSTIMULATION AND AUTOANTIGEN SPECIFICITY ENABLE B-CELLS TO ACTIVATE AUTOREACTIVE T-CELLS

This study examines the role of B cells as auto-APCs in activating aut oimmune T cell responses, Mice immunized with their own cytochrome c ( cyt c) elicit no detectable B or T cell responses, However, mice first primed with a cryptic self peptide, mouse cyt c 81-104, followed at 3 wk with a boost of whole cyt c, elicit autoreactive T cells specific to self cyt c, T cell autoimmunity is not elicited in similarly immuni zed B cell-deficient (mu MT) mice, The expression of the B7-2 and/or B 7-1 costimulatory molecules, as well as specificity to a self Ag, cyt c, enabled B cells to activate T cells to proliferate and to express I FN-gamma, IL-4, IL-5, and IL-10 cytokine mRNAs, In contrast, neither a doptively transferred B7(-) B cells nor nonspecific B7(+) B cells were able to activate naive T cells, Moreover, anti-B7-2 treatment of mice prevented the in vivo expression of the IL-4, IL-5, and IFN-gamma cyt okine mRNA responses, Our results suggest a major role of autoantigen- specific, B7-bearing B cells in breaking T cell tolerance to self Ag.