Antigen-initiated B lymphocyte differentiation. XX. Colony-forming B lymphocytes are not identical with the intermediate, "pre-progenitor" subset of primary or secondary B cells.

The surface immunoglobulin isotype and the cell cycle status of B lymphocyte agar-colony-forming cells (BL-CFC) were studied in order to test a hypothesis, based on their culture behavior, that they represent a mixture of virgin and memory "intermediate" or "pre-progenitor" B cells. If so, BL-CFC would be equivalent to the minor subset of B cells initiating adoptive immune responses. Most BL-CFC were found to be s-IgD+, whereas most progenitors of primary or secondary adoptive responses were s-IgD-. An intense nonspecific stimulus, in the form of horse erythrocytes injected i.p., failed to throw BL-CFC into cell cycle, as judged by hydroxyurea suicide experiments, whereas the progenitors of adoptive responses were thrown into cell cycle. It was concluded that BL-CFC as a whole were not "pre-progenitor" B cells, but more closely resembled the typical "direct progenitor" B cell. Some data derived from unprimed animals, namely, the level of dividing BL-CFC as assessed by hydroxyurea killing and sedimentation velocity distribution, together with the special sensitivity of even nondividing BL-CFC to killing by 3H-TdR, suggested that the agar culture system might select more activated B cells as colony formers.