The tumor necrosis factor (TNF) family member B cell activating factor (BAFF) binds B cells and enhances B cell receptor–triggered proliferation. We find that B cell maturation antigen (BCMA), a predicted member of the TNF receptor family expressed primarily in mature B cells, is a receptor for BAFF. Although BCMA was previously localized to the Golgi apparatus, BCMA was found to be expressed on the surface of transfected cells and tonsillar B cells. A soluble form of BCMA, which inhibited the binding of BAFF to a B cell line, induced a dramatic decrease in the number of peripheral B cells when administered in vivo. Moreover, culturing splenic cells in the presence of BAFF increased survival of a percentage of the B cells. These results are consistent with a role for BAFF in maintaining homeostasis of the B cell population.

Differences in the composition of the hepatitis C virus (HCV) quasispecies between plasma and blood mononuclear cells (BMC) strongly suggest that BMCs support viral replication. We examined the frequency of such compartmentalization, the cell types involved, the constraints exerted on the different variants, and the role of immunoglobulin-complexed variants. We screened the hypervariable region (HVR1) of HCV isolates from 14 HBsAg-and HIV-seronegative patients with chronic HCV infection. HCV RNA was amplified and cloned from plasma, the immunoglobulin G (IgG)-bound fraction, and total and sorted BMCs (CD19؉, CD8؉, CD4؉, and CD14؉ cells). Compartmentalization was estimated using a matrix correlation test. The ratio of nonsynonymous/synonymous substitutions (d N /d S ratio) was calculated for each compartment. HCV RNA was detected in 3/3 BMC, 11/11 CD19؉, 10/11 CD14؉, 4/11 CD8؉ and 0/11 CD4؉ cell samples. HVR1 sequences were significantly different between plasma and at least one cellular compartment in all nine cases analyzed, and between B cells (CD19؉) and monocytes ( H epatitis C virus (HCV) is an enveloped, positive-stranded RNA virus that circulates in vivo as a complex population of closely related variants referred to as a quasispecies. 1 Hepatitis C infection is frequently chronic, and its quasispecies nature probably plays a major role in viral persistence. 2,3 HCV genetic heterogeneity is particularly strong within a small hypervariable region (HVR1) that encodes a 27-amino acid peptide located at the N-terminus of the second envelope glycoprotein (E2) and is subjected to selective pressures by humoral and cellular immune responses. 4 One potential viral strategy explaining the persistence of HCV is infection of immune cells. Convincing evidence of HCV lymphotropism has been obtained in vitro in experiments showing that minor quasispecies components of strain H77 are selected in lymphoblastoid cell lines. 5 Subsequently, it was found that blood mononuclear cells (BMC) from chimpanzees that had been inoculated with this strain became infected by the same lymphotropic quasispecies components as those selected in vitro. 6 In vivo, HCV RNA has been detected in BMC by many teams. 7-14 Viral replication in these cells, shown by the detection of negatively stranded HCV RNA, an obligatory replication intermediate, generally occurs at a low level. 9,[15][16][17][18] Mutations in the 5Ј untranslated region-the viral internal ribosomal entry site-have been described in HCV strains isolated from BMCs. These mutations could influence the translational efficiency of the internal ribosomal entry site structure in lymphoblastoid cell lines 19 and point to HCV adaptation to BMCs. 6,20,21

The CD40 ligand (CD40L) is a transmembrane molecule of crucial interest in cell signaling in innate and adaptive immunity. It is expressed by a variety of cells, but mainly by activated T-lymphocytes and platelets. CD40L may be cleaved into a soluble form (sCD40L) that has a cytokine-like activity. Both forms bind to several receptors, including CD40. This interaction is necessary for the antigen specific immune response. Furthermore, CD40L and sCD40L are involved in inflammation and a panoply of immune related and vascular pathologies. Soluble CD40L is primarily produced by platelets after activation, degranulation and cleavage, which may present a problem for transfusion. Soluble CD40L is involved in adverse transfusion events including transfusion related acute lung injury (TRALI). Although platelet storage designed for transfusion occurs in sterile conditions, platelets are activated and release sCD40L without known agonists. Recently, proteomic studies identified signaling pathways activated in platelet concentrates. Soluble CD40L is a good candidate for platelet activation in an auto-amplification loop. In this review, we describe the immunomodulatory role of CD40L in physiological and pathological conditions. We will focus on the main signaling pathways activated by CD40L after binding to its different receptors.