Antigen-Independent Selection of T15 Idiotype During B-Cell Ontogeny In Mice

Precursors of B cells capable of responding to a T-independent form of phosphorylcholine (PC) in splenic focus assays were detected in the spleens of neonatal mice as early as 4 days after birth. The earliest anti-PC B cells were T15(-). T15(+) foci-forming B cells were first detected 6 days after birth and expanded rapidly to constitute greater than 80% of the total PC-specific foci by day 10. Injection of heat-killed S. pneumoniae (R36A) into neonatal mice resulted in priming of the antibody response to PC, with an idiotype profile reflecting that of precursors of foci-forming B cells at the time of antigen administration. Priming of 2-dayold mice with 2 X10(6) and 2 X10(7) R36A induced a five- and ten-fold increase in the antibody response to phosphorylcholine 6 to 8 weeks later. However, only 10 to 15% of the serum antibodies expressed the normally dominant T15 idiotype. Doses below 2 x10(5) R36A showed no detectable priming activity. PC-specific hybridomas derived from mice injected with 2 X10(7) R36A 2 days after birth lacked the idiotypic and molecular characteristics typical of T15(+) antibodies. Antibodies to phosphorylcholine, raised by immunization of 6-week-old mice are normally protective against pneumococcal infection. However, serum antibodies from mice treated with R36A 2 days after birth and responding to phosphorylcholine following challenge with R36A at 6 weeks of age failed to protect against deliberate infection with virulent S. pneumoniae. These observations imply that the antigen phosphorylcholine does not play a role in the selective expansion and dominant expression of the T15 idiotype.