A novel role for macrophages: The ability of macrophages to tolerize B cells

We investigated the ability of macrophages (Mφ) to present the tolerogen fluoresceinated sheep γ-globulin (FL-SGG) B cells. Mφ pulsed with FL-SGG or murine FL-IgG2 were able to tolerize normal spleen B cells specifically as assessed by the plaque-forming cell (PFC) response to the antigens FL-Brucella abortus (FL-BrA) and FL-polymerized flagellin (FL-POL). Tolerance was not induced when Mφ were pulsed with a variety of other FL antigens or the synthetic tolerogen FL-D-glutamic acid-D-lysine (FL-D[G,L]). the ability of Mφ to tolerize B cells was not T cell-dependent, because populations of both T-depleted B cells and hapten-specific B cells were tolerizable. Mφ-induced B cell tolerance did not exhibit genetic restriction with regard to the H-2 haplotype of the presenting Mφ or the responding B cells. A variety of different types of peritoneal Mφ, including normal resident Mφ and those elicited by thioglycollate or concanavalin A (the latter are predominantly Ia⁺), could tolerize B cells after being pulsed with FL-SGG. We compared tolerogen-pulsed Mφ to soluble tolerogen for the ability to tolerize B cells and found that tolerogen bound to Mφ was more than 10 times as potent as an equivalent amount of soluble tolerogen. In contrast to the ability of Mφ to present FL-SGG in a tolerogenic fashion to B cells, the P388AD lymphoid dendritic cell-like tumor line presented FL-SGG in an immunogenic mode to B cells. Tolerogen bound to P388AD cells could specifically augment a PFC response to both FL-BrA and FL-POL. We suggest that certain types of Mφ may play a role in unresponsiveness by enhancing the tolerogenicity of soluble antigen, whereas other accessory cells may present the same moieties in an immunogenic fashion.