Cellular events in tolerance. VI. Neonatal vs adult B cell tolerance: differences in antigen-binding cell patterns and lipopolysaccharide stimulation.

The numbers and fate of antigen-binding cells (ABC) in neonatal and adult mice rendered tolerant to fluorescein (FL)-labeled heterologous gamma-globulins were studied. Similar numbers of FL-ABC were observed 1 day after tolerogen in both adult and neonatal mouse spleens: by 7 days after tolerization, no FL-ABC were observed in either case. Reinjection with FL-tolerogen at 7 days led to the detection of normal numbers of ABC in adult mice but significantly reduced numbers in neonates. This suggests that neonatal ABC either have been deleted or have failed to resynthesize surface receptors. Two weeks after tolerance induction, spleen cells from these tolerant mice were cultured with Escherichia coli lipopolysaccharide (LPS), a polyclonal B cell mitogen, or with specific antigen. Tolerant adult spleen cells made an equivalent anti-FL response to that of the uninjected controls when stimulated with LPS, but were unresponsive to specific antigenic triggering. In contrast, spleen cells from neonatally tolerized mice were unresponsive to either specific or nonspecific (LPS) stimulation. Thus, these neonatally tolerized spleen cells lose sensitivity to polyclonal-stimulating agents (along with their receptors), or more simply, are deleted.