Isotype commitment in the in vivo immune responses. II. Polyclonal plaque-forming cell responses to lipopolysaccharide in the spleen and bone marrow.

Injection of lipopolysaccharide into adult mice results in a rapid increase in the number of splenic IgM-secreting plaque-forming cells (PFC) so that by 60 h they represent roughly 20 times those present in normal mice. Although inhibited for the first two days, IgG3, IgG2b and IgG2a PFC are later selectively stimulated and, by 110 h, they reach numbers that are 100, 40 and 30 times, respectively, those of normal mice. IgG1 PFC are stimulated only marginally and 48 h after the maximal responses of the other IgG subclasses. IgA PFC are selectively inhibited and drop to 20% of normal numbers 4 days after injection. The ability of lipopolysaccharide to selectively stimulate B cells for the production of IgG3, IgG2b and IgG2a was further substantiated by studying athymic mice, and by using adoptive cell transfers that overcome regulatory influences limiting these responses in intact mice. Under these conditions, 16% of all spleen cells are PFC and up to 85% of all Ig-secreting cells are included in those three isotypes. Similar responses are also detected in bone marrow but they occur 24-48 h after the splenic responses, suggesting that bone marrow PFC are not induced in situ. These results demonstrate a selective in vivo isotype commitment in response to lipopolysaccharide that is polyclonal and, therefore, independent of V region specificities.