Stimulation by T Cell Independent Antigens Can Relieve the Arrest of Differentiation of Immature Auto‐Reactive B Cells in the Bone Marrow *

The pair of μH‐chain and k L‐chain transgenes encoding the Sp6 TNP/DN A‐specific IgM was bred onto the rearrangement‐deficient genetic background of RAG‐2T mice, and onto the k L‐chain expression‐deficient background of iE k 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 k T mice were found to be similar to those of normal mice except that all sIg + cells expressed μL‐chains, of which 40% coexpressed the transgenic k L‐chain. It indicates that the repertoire of μL‐chain rearrangements and the μL‐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 μg/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.