Lin28b promotes fetal B lymphopoiesis through the transcription factor Arid3a.
Bottom Line: Here, we report key advances in our understanding of the regulation of B-1/B-2 development.Second, intact BCR signaling is required for the generation of B1a B cells from Lin28b-transduced BM progenitors, supporting a requirement for ligand-dependent selection, as is the case for normal B1a B cells.Third, the VH repertoire of Lin28b-induced BM B1a B cells differs from that of normal B1a, suggesting persisting differences from fetal progenitors.
Affiliation: Fox Chase Cancer Center, Philadelphia, PA 19111.Show MeSH
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Mentions: The generation of normal CD5+ B cells depends on the presence of antigen (Hayakawa et al., 1999). Furthermore, mouse mutants that weaken BCR signaling have a deficit in CD5+ B cells (Tarakhovsky et al., 1995; Inaoki et al., 1997; Suzuki et al., 1999). For example, the Btk-deficient Xid mouse has fewer B cells in spleen, accumulates B cells with a distinctive phenotype, has very low levels of serum IgM, and completely lacks CD5+ B cells (Hayakawa et al., 1983; Khan et al., 1995). However, the ability of ectopic expression of Lin28B to divert cells to the B-1 fate in progenitors with defective BCR signaling has never been directly tested. Therefore, we asked whether BCR signaling is required for production of Lin28b-induced BM-derived B1a B cells. For this purpose, transduced pro-B cell isolated from BM of Xid mice were transferred into SCID mice, and then engrafted cells were examined for generation of CD5+ B cells. As shown in Fig. 5 A, even provision of Lin28b did not induce production of CD5+ B cells from Btk-deficient pro-B cells, demonstrating a continuing dependence on intact (Btk dependent) BCR signaling.
Affiliation: Fox Chase Cancer Center, Philadelphia, PA 19111.