Suppression of B-cell differentiation by natural killer (asialo GM1+) cells in mice.
Mice were injected intravenously with rabbit antiserum to ganglio-n-tetraosylceramide (asialo GM1, ASGM1), a neutral glycosphingolipid present at high quantities on the surface of natural killer (NK) cells. Spleen cells prepared from the mice were then examined for NK activity against YAC-1 targets, for phagocytic cells and by flow cytometric analysis for Thy1, Lyt1, Lyt2, ASGM1 and surface Ig (SIg) phenotypes. Administration of anti-ASGM1 in mice resulted in a complete depletion of NK activity and ASGM+1 cells in the spleen, but no changes in the proportions of Thy1+ cells and their Lyt1+ and Lyt2+ subsets and phagocytic cells. Corresponding to this selective depletion of ASGM+1 cells and NK activity, the spleen cells showed an increased number of SIg+ B cells and augmented mitogenic responses to B-cell but not T-cell mitogens. These NK-depleted spleen cells also showed production of pokeweek mitogen (PWM)-driven plaque-forming cells (PFC) to much higher levels than those of control spleens. In the spleens of mice treated with varying concentrations of anti-ASGM+1, a good correlation was found between the decreased NK activity and the enhanced PFC response. To directly test the possible suppressor activity of NK cells on PWM-induced PFC response, NK (ASGM+1) cells were highly purified from the spleen by a combination of Percoll gradients and cytolysis of T cells by monoclonal antibodies followed by indirect panning. When added to NK-depleted spleen cells, they suppressed the augmented PFC response of NK-depleted spleen cells, depending on the number of cells added. These results suggest that NK (ASGM+1) cells in mice exhibit a suppressor property on B cells, which are undergoing spontaneous or mitogen-induced differentiation.
D000818:Animals; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002454:Cell Differentiation; D005677:G(M1) Ganglioside; D006028:Glycosphingolipids / Q000032:analysis / Q000276:immunology; D007108:Immune Tolerance; D007694:Killer Cells, Natural / Q000032:analysis / Q000502:physiology*; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D011043:Pokeweed Mitogens; D011947:Receptors, Antigen, B-Cell / Q000032:analysis; D013154:Spleen / Q000166:cytology / Q000276:immunology
D006028:Glycosphingolipids; D011043:Pokeweed Mitogens; D011947:Receptors, Antigen, B-Cell; D005677:G(M1) Ganglioside; C018835:asialo GM1 ganglioside