TOLEROGENICITY OF RESTING AND ACTIVATED B-CELLS

Antigen presentation by resting splenic B cells has been shown previou sly to induce T helper 1 cell (Th1) anergy. In contrast to expectation s, it was found here that B cells treated with F(ab')(2) goat anti-mou se immunoglobulin (IgM) for 24 or 48 h also presented antigen (Ag) to Th1 cells in a manner that induced dramatic Ag-specific proliferative inactivation. The tolerogenicity of the anti-Ig-treated B cells was co nsistent with the observation that these B cells were only slightly mo re efficient than resting B cells in stimulating human gamma globulin (HGG)-induced proliferation of HGG-specific Th1 cells in primary cultu res. The activated B cells were, however, more efficient than resting B cells in stimulating a primary mixed leukocyte reaction, and exhibit ed increased expression of major histocompatibility complex class II m olecules, RL388 Ag and transferrin receptor. In addition, unlike resti ng B cells, which expressed little detectable B7, ant-Ig-treated B cel ls expressed high levels of B7. The functional capacity of the B7 expr essed on the activated B cells was demonstrated by the fact that the A g-presenting capacity of these B cells was inhibited by the addition t o culture of CTLA4Ig, a soluble receptor for B7. It is unlikely that t he tolerogenicity of the activated B cells was due to an inability of the Th1 cells to respond to B7 signals; the Th1 clones used in the exp eriments, unlike the Th2 clones tested, expressed CD28, the ligand for B7. In addition, anti-CD28 monoclonal antibody inhibited the inductio n of Th1 cell anergy when added to cultures of Th1 cells and Ag-pulsed fixed antigen-presenting cells. Taken together, the results indicate that B cells, even when activated, do not satisfy the costimulatory re quirements of the Th1 cells used here, and therefore can present Ag in a tolerogenic fashion to Th1 cells. The costimulator deficiency of ac tivated B cells may reflect an inadequacy in the level of B7 expressed or a lack of some other molecule.