Restricted idiotypic profile of anti‐phosphorylcholine antibodies induced by carrier‐specific helper T cell clones

Abstract

The primary antibody response of C57BL/6 mice to phosphorylcholine (PC) is dominated by immunoglobulins of the T15 idiotype family. Using monoclonal antibodies that define individual idiotopes (Id) of T15, it has been shown that the antibody plaque-forming cells (PFC) arise from heterogeneous population of B cells that may express some but not all T15 Id. In the present study, we tested the ability of antigen (keyhole limpet hemocyanin, KLH)-specific CD4+ T cell clones (Th) to provide help for various T15 B cell subsets in response to PC-KLH in vitro. Four independently derived, KLH-specific Th clones were found to provide quantitative help (80-120 PFC/culture of 10(6) B cells) which was comparable to KLH-primed, unselected T cells. However, the response in the presence of the cloned T cells was idiotopically restricted: T15 idiotopes B24-44 and B36-75 were expressed on 60% to 90% PFC, whereas Id AB1-2 and B36-82 were not present (0%-20% PFC). All of these Id were highly expressed in cultures with KLH-primed, unselected splenic T cells. Evidently, the cloned Th cells provided help to only a subset of idiotypically distinct B cells. Bulk spleen T cells from unprimed donors by themselves did not provide any help for the primary response to PC-KLH. However, when these cells were added to the cultures containing B cells and KLH-specific Th clones, the repertoire of the response was fully restored, including the AB1-2/B36-82 Id (50%-80% PFC). These results suggest the existence of an auxiliary helper mechanism that may be required for activation of some B cells in addition to the antigen-specific Th cells.

Age‐related changes in antibody repertoire: contribution from T cells

“…Anti-idiotypic antibodies were used to analyze ilurepertoire of antibody response to the PC hapten (PC-KLH or PC-ovalbumin) with help provided by various carrier-primed TH populations in viiro. It was found that help from the bulk of splenic T cells stimulated a clonotypic anti-PC response which was very different from that stimulated by TH-cell clones; individual TH clones appeared to provide help for distinct PC-reactive B-cell clones (55)(56)(57). To explain such clonotype-specific help, one can envision that optimal stimulus for B-cell activation and growth reqtiires a balance between the strength of the Ig receptor-mediated signal, which depends on the affinity of germline-encoded sig, and the signals from the helper cells.…”