B cell participation in the recursive selection of T cell repertoires

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Abstract
Normal BALB/c mice produce 2,4,6-trinitrophenyl (TNP)-I-Ad specific T helper (Th) cells expressing a receptor heterodimer which share with anti-TNP antibodies an idiotope defined by the F6(51) anti-idiotypic antibody. Expression of this Th idiotype is controlled by major histocompatibility complex and immunoglobulin heavy chain-linked genes and results from antibody-dependent selection of T cell repertoires (Martinez-A. et al., Eur. J. Immunol. 1986. 16: 417). We now present evidence for the recursive nature of T → B cell repertoire selection and suggest that perinatal B cells, present in adult peritoneal cavity, operate in the early phases of this process. Thus, the Th idiotype is absent in BALB/c mice which are either suppressed from birth with anti-p antibodies, or reconstituted with autologous bone marrow after lethal irradiation as adults. Supplementation of bone marrow reconstitution with syngeneic Thy-1−, Ly-1+ peritoneal B cells, however, selects Th cell repertoires that are undistinguishable from normal mice as to expression of the F6 (51) clonotype. This effect is lost after depletion of Ly-1− cells in the reconstituting Thy-1− peritoneal cell population. Interestingly, large in vivo “naturally” activated Ly-1− splenic B cells can also reconstitute Th idiotype expression if they .are isolated from normal, but not from athymic, nude donors. However, transfer of normal large splenic T cells to adult nude mice “educates” the splenic “large B cell” compartment in these animals such that they acquire the ability to recursively select, upon transfer to bone marrow reconstituted recipients, the Th clonotype. Small resting lymphocytes in either the B or T cell lineage fail to exert these selective effects. These observations constitute formal evidence for recursive repertoire selection in the naturally activated lymphocyte compartment of normal animals.