B cells and osteoblast and osteoclast development.

The molecules that regulate bone cell development, particularly at the early stages of development, are only partially known. Data are accumulating that indicate a complex relationship exists between B cells and bone cell differentiation. Although the exact nature of this relationship is still evolving, it takes at least two forms.

Pax5-deficient mice exhibit early onset osteopenia with increased osteoclast progenitors.

Pax5 encodes BSAP, a member of the paired box domain transcription factors, whose expression is restricted to B lymphocyte lineage cells. Pax5(-/-) mice have a developmental arrest of the B cell lineage at the pro-B cell stage. We show here that Pax5(-/-) mice are severely osteopenic, missing 60% of their bone mass.

B cell-specific loss of histone 3 lysine 9 methylation in the V(H) locus depends on Pax5.

Immunoglobulin heavy chain rearrangement (V(H)-to-DJ(H)) occurs only in B cells, suggesting it is inhibited in other lineages. Here we found that in the mouse V(H) locus, methylation of lysine 9 on histone H3 (H3-K9), a mark of inactive chromatin, was present in non-B lineage cells but was absent in B cells. As others have shown that H3-K9 methylation can inhibit V(D)J recombination on engineered substrates, our data support the idea that H3-K9 methylation inhibits endogenous V(H)-to-DJ(H) recombination.

Evidence for a dual pathway of activation in CD43-stimulated Th2 cells: differential requirement for the Lck tyrosine kinase.

CD43 is the most abundant cell surface-expressed sialoglycoprotein on T lymphocytes. Despite evidence demonstrating the activation of some signaling components by CD43, the exact function of CD43 in T cell biology remains controversial. In this study, we demonstrate that the sole ligation of CD43 in cloned Th2 cells resulted in cytokine production, cellular proliferation, and upregulation of CD25 and CD69 activation markers.

Pax5 is required for recombination of transcribed, acetylated, 5' IgH V gene segments.

Pax5-deficient progenitor B (pro-B) cells are thought to be severely defective for recombination of all immunoglobulin heavy chain (IgH) V gene segments, but the mechanism by which Pax5 regulates this process has not been defined. To address this issue, we have examined the assembly of the IgH locus in Pax5-deficient pro-B cells and find, unexpectedly, that 3' IgH V gene segments, which lie closest to the D-J-Cmu region, recombine efficiently, but progressively more distal V gene segments recombine progressively less efficiently. Histone acetylation and germ-line transcription correlate strongly with an open or an accessible chromatin structure thought to be permissive for V(D)J recombination, and defects in recombination are typically accompanied by deficits in these processes.

Ly-6 superfamily members Ly-6A/E, Ly-6C, and Ly-6I recognize two potential ligands expressed by B lymphocytes.

Most hemopoietic cells express one or more members of the Ly-6 supergene family of small glycosylphosphatidylinositol-linked proteins. Although levels of Ly-6 proteins vary with stages of differentiation and activation, their function largely remains unknown. To ascertain whether ligands for Ly-6 proteins exist, chimeric proteins were constructed in which Ly-6E, Ly-6C, and Ly-6I were fused to the murine IgM heavy chain.