Anti-immunoglobulin stimulation of murine lymphocytes. VII. Identification of an age-dependent change in accessory cell function.

Rabbit anti-mouse immunoglobulin-induced proliferation of murine B cells requires the participation of a macrophage- (M phi)like accessory cell. This cell is found in the spleen of aged mice, the B cells of which respond to stimulation by intact anti-Ig molecules. M phi characteristics of this cell include resistance to treatment with either anti-theta or anti-Ig plus complement, adherence to plastic, and resistance to radiation. Evidence was obtained that indicates that the age-dependent anti-Ig responsiveness of B cells involves, in part, a temporal change in the splenic M phi population. The ability of these accessory cells to facilitate anti-Ig responsiveness by normally unresponsive B cells was shown both in vivo and in vitro. Reconstitution of lethally irradiated aged, but not young, mice with spleen cells from unresponsive young mice resulted in the appearance of anti-Ig responsive B cells within 30 days. Similarly, coculture of unresponsive spleen cells with irradiated splenic adherent cells from aged, but not young, mice provided accessory cell activity for anti-Ig responses. Additional experiments showed that accessory cells were also present in bone marrow and the peritoneal cavity but were absent in lymph node and thymus. Addition of 2-mercaptoethanol to the culture medium functionally replaced the requirement for accessory cells and was also found to alter the response pattern of the B cells.