SYK Inhibition Induces Apoptosis in Germinal Center-Like B Cells by Modulating the Antiapoptotic Protein Myeloid Cell Leukemia-1, Affecting B-Cell Activation and Antibody Production.

B cells play a major role in the antibody-mediated rejection (AMR) of solid organ transplants, a major public health concern. The germinal center (GC) is involved in the generation of donor-specific antibody-producing plasma cells and memory B cells, which are often poorly controlled by current treatments. Myeloid cell leukemia-1 (Mcl-1), an antiapoptotic member of the B-cell lymphoma-2 family, is essential for maintenance of the GC reaction and B-cell differentiation.

Subcellular localization of PUMA regulates its pro-apoptotic activity in Burkitt's lymphoma B cells.

The BH3-only protein PUMA (p53-upregulated modulator of apoptosis) is a major regulator of apoptosis. It belongs to the Bcl-2 family of proteins responsible for maintaining mitochondrial outer membrane integrity by controlling the intrinsic (mitochondrial) apoptotic pathway. We describe here a new pathway regulating PUMA activation through the control of its subcellular distribution.

MAVS ubiquitination by the E3 ligase TRIM25 and degradation by the proteasome is involved in type I interferon production after activation of the antiviral RIG-I-like receptors.

Background: During a viral infection, the intracellular RIG-I-like receptors (RLRs) sense viral RNA and signal through the mitochondrial antiviral signaling adaptor MAVS (also known as IPS-1, Cardif and VISA) whose activation triggers a rapid production of type I interferons (IFN) and of pro-inflammatory cytokines through the transcription factors IRF3/IRF7 and NF-κB, respectively. While MAVS is essential for this signaling and known to operate through the scaffold protein NEMO and the protein kinase TBK1 that phosphorylates IRF3, its mechanism of action and regulation remain unclear.

Results: We report here that RLR activation triggers MAVS ubiquitination on lysine 7 and 10 by the E3 ubiquitin ligase TRIM25 and marks it for proteasomal degradation concomitantly with downstream signaling.

Changes in blood B cell phenotypes and Epstein-Barr virus load in chronically human immunodeficiency virus–infected patients before and after antiretroviral therapy.

Background: Switched and nonswitched memory B cells, which usually constitute the main reservoirs of Epstein‐Barr virus (EBV), are rapidly depleted in patients with chronic human immunodeficiency virus (HIV) infection. Because the EBV load is frequently increased in these patients, other B cell reservoirs might participate in EBV persistence.

Methods: We examined the combined expression of CD27, SIgD/G/M, CD38, CD10, CD5, CXCR5, CD62L, CD44, and CXCR3 on B cells from healthy donors (n = 30) and from HIV type 1-infected patients (n = 23) at diagnosis and after highly active antiretroviral therapy.

Serum leptin in patients with alcoholic liver disease.

Background: The mechanisms by which overweight makes the liver more susceptible to alcoholic liver injury remain to be determined. Therefore, we conducted the following studies to further elucidate the role of leptin in the pathogenesis of steatosis and cirrhosis caused by chronic alcohol consumption in human beings.

Methods: Two-hundred nine consecutive patients with alcoholic liver disease were studied.

Balance between pro and anti-inflammatory cytokines in patients with acute alcoholic hepatitis.

Unlabelled: The ability of endogenous IL-10 to modulate inflammatory response and to limit hepatotoxicity has been shown in several models of liver injury.

Aims: The objectives of this study were to evaluate the relationship between liver disease and the balance between pro and anti-inflammatory cytokines in acute alcoholic hepatitis.

Methods: Twenty-five patients with pure steatosis, 17 with cirrhosis and mild acute alcoholic hepatitis (discriminant function value<32) and 41 patients with cirrhosis and severe acute alcoholic hepatitis (discriminant function value >=32) were studied.

Abnormal production of the TNF-homologue APRIL increases the proliferation of human malignant glioblastoma cell lines via a specific receptor.

A proliferation-inducing ligand (APRIL) of the tumour necrosis factor (TNF) family is produced in small amounts in many tissues and more abundantly in tumours. APRIL has been reported to promote cell growth in vivo and in vitro. It was recently shown that the production of APRIL in some glioblastoma cell lines does not lead to an increase in cell growth.

Role of the chemokine stromal cell-derived factor 1 in autoantibody production and nephritis in murine lupus.

In normal mice, stromal cell-derived factor 1 (SDF-1/CXCL12) promotes the migration, proliferation, and survival of peritoneal B1a (PerB1a) lymphocytes. Because these cells express a self-reactive repertoire and are expanded in New Zealand Black/New Zealand White (NZB/W) mice, we tested their response to SDF-1 in such mice. PerB1a lymphocytes from NZB/W mice were exceedingly sensitive to SDF-1.

Synthesis of glucocorticoid-induced leucine zipper (GILZ) by macrophages: an anti-inflammatory and immunosuppressive mechanism shared by glucocorticoids and IL-10.

Glucocorticoids and interleukin 10 (IL-10) prevent macrophage activation. In murine lymphocytes, glucocorticoids induce expression of glucocorticoid-induced leucine zipper (GILZ), which prevents the nuclear factor kappaB (NF-kappaB)-mediated activation of transcription. We investigated whether GILZ could account for the deactivation of macrophages by glucocorticoids and IL-10.

CX(3)C chemokine fractalkine in pulmonary arterial hypertension.

Perivascular infiltrates composed of macrophages and lymphocytes have been described in lung biopsies of patients displaying pulmonary arterial hypertension (PAH), suggesting that circulating inflammatory cells can be recruited in affected vessels. CX(3)C chemokine fractalkine is produced by endothelial cells and promotes leukocyte recruitment, but unlike other chemokines, it can capture leukocytes rapidly and firmly in an integrin-independent manner under high blood flow. We therefore hypothesized that fractalkine may contribute to pulmonary inflammatory cell recruitment in PAH.

Interleukin-10 modulates the sensitivity of peritoneal B lymphocytes to chemokines with opposite effects on stromal cell-derived factor-1 and B-lymphocyte chemoattractant.

Interleukin-10 (IL-10) is constitutively produced by peritoneal B1a lymphocytes, and stromal cell-derived factor-1 (SDF-1) by mesothelial cells. Independent studies have shown that both IL-10 and SDF-1 are involved in the persistence of the peritoneal B-lymphocyte compartment. This study shows that IL-10 and SDF-1 act in synergy on peritoneal B lymphocytes.