Anti-immunoglobulin (anti-Ig) antibodies can stimulate B cell proliferation in spleen cell cultures from aged (greater than 7 to 9 months) but not young (less than 5 to 7 months) mice. The response appears to be T-independent since anti-θ and complement treatment did not diminish responsiveness of B cells from aged mice. The lack of responsiveness of spleen cells from young mice is not due to suppressor T cells: 1) T cell-depleted, B cell-enriched cultures of spleen cells from young mice remained unresponsive to anti-Ig and 2) responsiveness of B cells from aged mice was not suppressed by co-culture with spleen cells, purified splenic T cells, or thymocytes from young mice.
Additional experiments in which the stimulating ability of intact anti-Ig was compared to its Fab′2 counterpart (Fab′2 anti-Ig) revealed two significant findings. First, B cells from young mice that are normally unresponsive to intact anti-Ig were found to respond quite well to Fab′2 anti-Ig. This response, measured at 72 hr of culture, was profoundly inhibited by intact anti-Ig, even when the latter was added at 48 hr. This indicates that active B cell proliferation can be inhibited by interactions of anti-Ig molecules with Fc receptors. Second, B cells from aged mice were found to respond significantly better to Fab′2 anti-Ig than to the intact molecule. However, addition of intact anti-Ig to these Fab′2-stimulated cultures resulted in relatively poor inhibition of the response. These results indicate that the ability of mouse B cells to respond to anti-Ig is related to the efficiency of Fc receptors in mediating inhibitory signals and further suggest that the aging process in the mouse is accompanied by a decline in B cell regulation intrinsic to the B cell itself.
This work was supported in part by National Institutes of Health Grants AG-00464, AI-00013, and AI-12993.