Analysis of the role of IL-21 in development of murine B cell progenitors in the bone marrow.

IL-21 plays a key role in the late stage of B cell development, where it has been shown to induce growth and differentiation of mature B cells into Ig-secreting plasma cells. Because IL-21R has also been reported on bone marrow (BM) B cell progenitors, we investigated whether IL-21R influenced earlier stages of B cell development. IL-21R is functional as early as the pro-B cell stage, and the strength of receptor-mediated signaling increases as cells mature.

Early B-cell factor regulates the expression of Hemokinin-1 in the olfactory epithelium and differentiating B lymphocytes.

Hemokinin-1, encoded by the TAC4 gene, is a tachykinin most closely related to substance P. Previous studies have shown that TAC4 distinguishes itself from other tachykinins by its predominantly non-neuronal expression profile, particularly in cells of the immune system. Here we report for the first time that the highest levels of TAC4 expression are found in the olfactory epithelium.

Targeted deletion of the tachykinin 4 gene (TAC4-/-) influences the early stages of B lymphocyte development.

Hemokinin-1 (HK-1), encoded by the TAC4 gene, is a tachykinin peptide that is predominantly expressed in non-neuronal cells, such as immune cells. We have disrupted the mouse TAC4 gene to obtain a better understanding of the actions of HK-1 during hematopoiesis. We demonstrate here that TAC4(-/-) mice exhibit an increase of CD19(+)CD117(+)HSA(+)BP.

Antimicrobial properties of hemokinin-1 against strains of Pseudomonas aeruginosa.

Aims: In this study, we examined whether hemokinin-1, the newest member of the tachykinin family and a close relative of substance P, has antimicrobial properties which have been attributed to other neuropeptides including substance P.

Main Methods: Top agar assays were performed to determine the antimicrobial activity of hemokinin-1 and substance P against various microorganisms.

Key Findings: Here we provide evidence that hemokinin-1 peptide possesses antimicrobial properties against some strains of Pseudomonas aeruginosa, while substance P was only marginally effective.

Regulatory mechanisms in the differential expression of Hemokinin-1.

Hemokinin-1, encoded by the TAC4 gene, is the most recent addition to the tachykinin family. Although most closely related to the neuropeptide Substance P, Hemokinin-1 distinguishes itself from other tachykinins by its predominantly non-neuronal expression pattern. Its expression in T and B lymphocytes, macrophages, and dendritic cells points to an important role for Hemokinin-1 in the immune system.

Co-regulated decrease of Neurokinin-1 receptor and Hemokinin-1 gene expression in monocytes and macrophages after activation with pro-inflammatory cytokines.

Hemokinin-1 (HK-1), a potent ligand for the Neurokinin-1 receptor (NK-1) is thought to play a role in the immune system. To investigate the regulation of this receptor-ligand pair, we examined the effects of pro-inflammatory cytokines on their expression in the monocyte/macrophage cell lines Wehi-3 and RAW264.7.

Murine model of immune-mediated rejection of the acute lymphoblastic leukemia 70Z/3.

70Z/3 is a murine pre-B cell leukemia line derived from BDF(1) mice and has been used in the study of signaling pathways in B cells. 70Z/3 cells were initially found to cause widespread disease upon injections in animals. We have isolated 70Z/3 variants divergent in their capacity to lead to morbidity after injections.

Identification of potential regulatory elements in the human immunoglobulin loci.

In this post-genomic era, it is necessary to formulate specific questions and develop bioinformatics tools to understand the vast amounts of information stored in DNA sequence. Using the combinatorial pattern discovery algorithm called Teiresias developed by the Bioinformatics and Pattern Discovery Group at IBM, we have identified novel conserved motifs present in the immunoglobulin loci. In the human VH promoter regions, two new putative regulatory elements have been implicated in basal transcriptional regulation of immunoglobulin.