A novel role for macrophages: the ability of macrophages to tolerize B cells.
We investigated the ability of macrophages (M phi) to present the tolerogen fluoresceinated sheep gamma-globulin (FL-SGG) to B cells. M phi 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 M phi 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 M phi to tolerize B cells was not T cell-dependent, because populations of both T-depleted B cells and hapten-specific B cells were tolerizable. M phi-induced B cell tolerance did not exhibit genetic restriction with regard to the H-2 haplotype of the presenting M phi or the responding B cells. A variety of different types of peritoneal M phi, including normal resident M phi and those elicited by thioglycollate or concanavalin A (the latter are predominantly la+), could tolerize B cells after being pulsed with FL-SGG. We compared tolerogen-pulsed M phi to soluble tolerogen for the ability to tolerize B cells and found that tolerogen bound to M phi was more than 10 times as potent as an equivalent amount of soluble tolerogen. In contrast to the ability of M phi 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 M phi 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.
D000818:Animals; D000941:Antigens / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D019793:Fluorescein; D005452:Fluoresceins; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D007108:Immune Tolerance; D007140:Immunoglobulin Fab Fragments / Q000378:metabolism; D007700:Kinetics; D008211:Lymphocyte Cooperation; D008264:Macrophages / Q000276:immunology* / Q000502:physiology; D008297:Male; D051379:Mice; D008806:Mice, Inbred AKR; D051381:Rats; D011917:Rats, Inbred Lew; D013045:Species Specificity; D013154:Spleen / Q000166:cytology; D005719:gamma-Globulins / Q000276:immunology
D000941:Antigens; D005452:Fluoresceins; D000949:Histocompatibility Antigens Class II; D007140:Immunoglobulin Fab Fragments; D005719:gamma-Globulins; D019793:Fluorescein