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

Abstract

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 and 2 X10 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 xl0 R36A showed no detectable priming activity. PC-specific hybridomas derived from mice injected with 2 X10 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.

The Autoreactivity of Anti-Phosphorylcholine Antibodies for Atherosclerosis-Associated Neo-Antigens and Apoptotic Cells

“…Murine B cells expressing transgenes for group I anti-PC Abs have also been reported to display altered activation, trafficking, and peripheral accumulation (19), which may suggest that these Ig transgene-expressing B cells were being selected by an autoantigen. However, until our recent demonstration of PC neo-determinants on apoptotic cells and on atherosclerosis-associated oxidation-specific Ags (20), the true nature of such postulated selecting self-Ags was unsuspected (21).…”

Functional Relationship Between T15 and J558 Idiotypes in BALB/c Mice

“…6B) (Vakil et al, 1991) clones increase in frequency while others decline our facility. (Sigal et al, 1977;Stohrer and Kearney, 1984;Vakil et al, 1991 …”

“…In a similar experiment, mice were stration of soluble idiotype-bearing immunoinjected with 5/g of DEX on days 2, 7, 14, or 21 globulins would block signaling through B-cellafter birth and challenged with R36A and DEX at 8 associated idiotypes on the precursors of endoweeks of age (Fig. 6B) (Vakil et al, 1991) clones increase in frequency while others decline our facility. (Sigal et al, 1977;Stohrer and Kearney, 1984;Vakil et al, 1991 …”

Immune recognition of OxLDL in atherosclerosis

“…This model suggests a possible mechanism by which multispecific T15 + B-cell clones may have been positively selected. These clones, which react not only with OxLDL and bacterial PC but also with apoptotic cells, may have been selected by interaction with apoptotic debris at sites of B-cell development in fetal liver and bone marrow (15), in a process that could involve receptor editing before or during the proliferation of specific B cells. Although the present authors have previously shown (16,17) that deliberate immunization of hypercholesterolemic rabbits or mice expressing high levels of OxLDL lessens atherosclerosis, the role of these autoantibodies against OxLDL needs more evaluation.…”