Stimulation by T cell independent antigens can relieve the arrest of differentiation of immature auto-reactive B cells in the bone marrow.

Abstract

The pair of microH-chain and kappa L-chain transgenes encoding the Sp6 TNP/DNA-specific IgM was bred onto the rearrangement-deficient genetic background of RAG-2T mice, and onto the kappa L-chain expression-deficient background of iE kappa T mice. Bone marrow of Sp6 transgenic RAG-2T mice contained normal numbers of B220(CD45R)+c-kit+ pro/preB-I-like cells and normal numbers of B220(CD45R)+TAC+ preB-II-like cells. Most strikingly, the numbers of immature sIgM+ B cells in the bone marrow were at least five-fold lower than normal, while mature B cells were almost undetectable in bone marrow as well as spleen. Hence, B cell development in these mice appears to be arrested at the transition from preB-II to immature B cells. The contents of bone marrow and spleen of the different precursors, immature and mature B cell compartments in Sp6iE kappa T mice were found to be similar to those of normal mice except that all sIg+ cells expressed lambda L-chains, of which 40% coexpressed the transgenic kappa L-chain. It indicates that the repertoire of lambda L-chain rearrangements and the lambda L-chains expressed from it suffices to relieve the arrest of differentiation seen in Sp6RAG-2T mice. The T cell-independent antigen TNP-Ficoll elicited within 5 days a response of the Sp6RAG-2T mice to develop to IgM-secreting cells and to fill the serum pool with the Sp6 transgenic IgM to 100 micrograms/ml, i.e. to normal serum levels of IgM in normal mice. TNP-Ficoll appears to interfere with the arrest of differentiation. Two scenarios for this arrest of differentiation and its relief by the T-independent antigen TNP-Ficoll are discussed.