Reversion of B cell commitment upon loss of Pax5 expression.

The transcription factor Pax5 is essential for initiating B cell lineage commitment, but its role in maintaining commitment is unknown. Using conditional Pax5 inactivation in committed pro-B cells, we demonstrate that Pax5 is required not only to initiate its B lymphoid transcription program, but also to maintain it in early B cell development. As a consequence of Pax5 inactivation, previously committed pro-B cells regained the capacity to differentiate into macrophages in vitro and to reconstitute T cell development in vivo in RAG2-/- mice.

The transcriptional repressor CDP (Cutl1) is essential for epithelial cell differentiation of the lung and the hair follicle.

The mammalian Cutl1 gene codes for the CCAAT displacement protein (CDP), which has been implicated as a transcriptional repressor in diverse processes such as terminal differentiation, cell cycle progression, and the control of nuclear matrix attachment regions. To investigate the in vivo function of Cutl1, we have replaced the C-terminal Cut repeat 3 and homeodomain exons with an in-frame lacZ gene by targeted mutagenesis in the mouse. The CDP-lacZ fusion protein is retained in the cytoplasm and fails to repress gene transcription, indicating that the Cutl1(lacZ) allele corresponds to a null mutation.

Pax5/BSAP maintains the identity of B cells in late B lymphopoiesis.

The B lineage commitment factor Pax5 (BSAP) is expressed throughout B cell development. To investigate its late function, we generated a mouse strain carrying a floxed Pax5 allele that was conditionally inactivated by CD19-cre or Mx-cre expression. Pax5 deletion resulted in the preferential loss of mature B cells, inefficient lymphoblast formation, and reduced serum IgG levels.

Pax5 determines the identity of B cells from the beginning to the end of B-lymphopoiesis.

Despite being one of the most intensively studied cell types, the molecular basis of B cell specification is largely unknown. The Pax5 gene encoding the transcription factor BSAP is required for progression of B-lymphopoiesis beyond the pro-B cell stage. Pax5-deficient pro-B cells are, however, not yet committed to the B-lymphoid lineage, but instead have a broad lymphomyeloid developmental potential.

IL-8 derivatives with a reduced potential to form homodimers are fully active in vitro and in vivo.

Interleukin 8 (IL-8) is a member of the CXC subfamily of chemokines which attracts and activates preferentially neutrophilic granulocytes. At nanomolar concentrations monomeric and dimeric forms of the molecule are in equilibrium, with the monomer being the prevalent form. Five amino acids from position 23 to 29 of the 72-amino acid IL-8 sequence form the dimer interface, with Leu25 and Val27 being highly conserved among the CXC chemokines.

Structure and activity of a chimeric interleukin-8-melanoma-growth-stimulatory-activity protein.

A 72-amino-acid chimeric protein, Chi1, was constructed from the N-terminal part of interleukin 8, IL-8-(1-53), and the C-terminal part of melanoma growth stimulatory activity, MGSA-(54-72). Chi1 protein showed receptor-binding specificity and biological activity similar, but not identical to IL-8 and decidedly different from MGSA. The structure of Chi1 was determined in solution by two-dimensional NMR and molecular-dynamics calculations.