Interleukin-10 modulates the sensitivity of peritoneal B lymphocytes to chemokines with opposite effects on stromal cell-derived factor-1 and B-lymphocyte chemoattractant. (17/214)

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. Indeed, autocrine production of IL-10 was absolutely required for all effects of SDF-1 on these cells, including increased proliferation, survival, and chemotaxis. Moreover, adding IL-10 to peritoneal B lymphocytes increased the effects of SDF-1. Neither IL-5, IL-6, nor IL-9 affected the response of peritoneal B lymphocytes to SDF-1. IL-10 was chemokinetic for peritoneal B lymphocytes, increasing their random mobility. It also potentiated the SDF-1-induced reorganization of the cytoskeleton without affecting CXCR4 gene expression by peritoneal B lymphocytes. Despite its chemokinetic properties, IL-10 abolished the migration of peritoneal B lymphocytes in response to B-lymphocyte chemoattractant (BLC), a chemokine targeting B lymphocytes to lymphoid organ follicles. The ability of B1a lymphocytes to produce IL-10 constitutively, combined with the opposite effects of this cytokine on the responses to SDF-1 and BLC, may account for the selective accumulation of B1 lymphocytes in body cavities.  (+info)

CXCL13 is required for B1 cell homing, natural antibody production, and body cavity immunity. (18/214)

B1 cells are a predominant cell type in body cavities and an important source of natural antibody. Here we report that in mice lacking the chemokine, CXCL13, B1 cells are deficient in peritoneal and pleural cavities but not in spleen. CXCL13 is produced by cells in the omentum and by peritoneal macrophages, and in adoptive transfers, B1 cells home to the omentum and the peritoneal cavity in a CXCL13-dependent manner. CXCL13(-/-) mice are deficient in preexisting phosphorylcholine (PC)-specific antibodies and in their ability to mount an anti-PC response to peritoneal streptococcal antigen. These findings provide insight into the mechanism of B1 cell homing and establish a critical role for B1 cell compartmentalization in the production of natural antibodies and for body cavity immunity.  (+info)

BCR ligation reprograms B cells for migration to the T zone and B-cell follicle sequentially. (19/214)

We have studied the impact of B-cell receptor (BCR) or CD40 ligation on the in vitro chemotactic response of tonsillar B cells to 4 chemokines: stromal cell-derived factor (SDF)-1alpha, macrophage inflammatory protein (MIP)-3alpha, MIP-3beta, and B-cell-attracting chemokine (BCA)-1. In the tonsil, SDF-1 and MIP-3alpha are both expressed in the crypt epithelium, while MIP-3beta is found in the T zone and BCA-1 in the follicles. Resting virgin and memory B cells display a similar chemotaxis pattern, and they both have the potential to migrate in vitro to all 4 chemokines studied. This pattern of responsiveness is strongly modified by a surrogate antigen (Ag) but is not altered by CD40 ligand. We report here that surrogate Ag induces a profound and sustained suppression of the response to the crypt chemokines SDF-1alpha and MIP-3alpha, while it exacerbates the migratory response to MIP-3beta. The effect of surrogate Ag on the response to BCA-1 is biphasic: After an initial phase of suppression, chemotaxis toward BCA-1 is strongly up-regulated. Our results suggest that Ag is primarily responsible for reprogramming the B-cell chemotaxis responsiveness during the humoral response. We propose that it initiates an ordered change of the chemotaxis machinery allowing Ag-activated B cells to relocate in the T zone and B-cell follicles sequentially.  (+info)

CXCR5-transduced bone marrow-derived dendritic cells traffic to B cell zones of lymph nodes and modify antigen-specific immune responses. (20/214)

Skin-derived migratory dendritic cells (DC), in contrast to bone marrow-derived DC (BMDC), express CXCR5, respond to the chemokine CXC ligand 13 (CXCL13) in vitro, and are capable of migrating to B cell zones (BCZ) in lymph nodes (LN) in vivo. Herein, we analyzed the surface phenotype of skin-derived migratory DC and found that 15-35% of MHC class II(high) cells showed high levels of expression of CXCR5 but expressed low levels of DEC205, a suggested characteristic of dermal-type DC in mice. To study the effects of CXCR5 on the trafficking dynamics of DC, we stably expressed CXCR5 in BMDC by retroviral gene transduction. CXCR5 was detected by flow cytometry on transduced cells, which responded to CXCL13 in vitro in chemotaxis assays (3-fold over nontransduced BMDC, p < 0.01). When injected into the footpads of mice, approximately 40% of injected CXCR5-BMDC were observed in BCZ of draining LN. Mice were vaccinated with CXCR5- and vector-BMDC that were pulsed with keyhole limpet hemocyanin (KLH) to induce Ag-specific cellular and humoral immune responses. Mice injected with CXCR5-BMDC (vs vector-BMDC) demonstrated marginally less footpad swelling in response to intradermal injection of KLH. Interestingly, significantly higher levels of KLH-specific IgG (p < 0.05) and IgM (p < 0.01) were found in the serum of mice injected with CXCR5-BMDC compared with mice immunized with vector-transduced BMDC. Thus, CXCR5 is predominantly expressed by dermal-type DC. Moreover, CXCR5 directs BMDC to BCZ of LN in vivo and modifies Ag-specific immune responses induced by BMDC vaccination.  (+info)

B cells control the migration of a subset of dendritic cells into B cell follicles via CXC chemokine ligand 13 in a lymphotoxin-dependent fashion. (21/214)

Certain classes of dendritic cells (DCs) meet rare cognate Ag-specific T and B cells inside primary B cell follicles for the development of germinal centers. However, the mechanisms underlying this coordination are still undefined. Cysteine-rich (CR) domain of the mannose receptor (CR-Fc)(+) DCs are a newly discovered subset of DCs that migrate rapidly into the primary lymphoid follicles from marginal zone after immunization. In this work, we uncover the key role of B cells in the establishment of a microenvironment that allows these DCs to be in the B cell area in a lymphotoxin (LT)-dependent fashion. CR-Fc(+) DCs are absent from the spleens of both LTbetaR- and LTalpha-deficient mice, suggesting that signaling by membrane LT is required for the presence of CR-Fc(+) DCs in the spleen. Interestingly, analysis of mutant mice that lack T, B, or NK cells demonstrates that B cell-derived membrane LT is essential for the unique localization of CR-Fc(+) DCs in the spleen. Using bone marrow transfer and ligand-blocking approaches, we provide evidence that B cell-derived LT acts indirectly on CR-Fc(+) DCs through LTbetaR(+) stromal cells. In analogous fashion to certain Ag-activated T and B cells, CR-Fc(+) DCs, expressing CXCR5, localize to primary lymphoid follicles in response to CXC ligand 13 (B lymphocyte chemoattractant). Together, we propose that B cells play a central role in establishing the chemotactic gradient that attracts not only Ag-activated T and B cells but also Ag-carrying CR-Fc(+) DCs. In turn, CR-Fc(+) DCs and T cells home to B cell follicles to interact with B cells in the developing germinal center.  (+info)

Chemokine requirements for B cell entry to lymph nodes and Peyer's patches. (22/214)

B cell entry to lymph nodes and Peyer's patches depends on chemokine receptor signaling, but the principal chemokine involved has not been defined. Here we show that the homing of CXCR4-/- B cells is suppressed in CCL19 (ELC)- and CCL21 (SLC)-deficient paucity of lymph node T cells mice, but not in wild-type mice. We also find that CXCR4 can contribute to T cell homing. Using intravital microscopy, we find that B cell adhesion to high endothelial venules (HEVs) is disrupted when CCR7 and CXCR4 are predesensitized. In Peyer's patches, B cell entry is dependent on CXCR5 in addition to CCR7/CXCR4. CXCL12 (SDF1) is displayed broadly on HEVs, whereas CXCL13 (BLC) is found selectively on Peyer's patch follicular HEVs. These findings establish the principal chemokine and chemokine receptor requirements for B cell entry to lymph nodes and Peyer's patches.  (+info)

Homing chemokines in rheumatoid arthritis. (23/214)

In about 20% of patients with rheumatoid arthritis, B and T lymphocytes recruited into the inflamed synovium are organized into complex microstructures, which resemble secondary lymphoid organs. The development of such lymphoid aggregates with germinal centers appears to contribute to the pathogenesis of the disease. Growing evidence indicates that chemokines and their receptors control the recruitment and positioning of leukocytes as well as their organization into node-like lymphoid structures. Here, we comment on recent studies highlighting the importance of chemokines in rheumatoid arthritis, in particular of B-cell-activating chemokine-1 in lymphoid neogenesis in the inflamed synovium.  (+info)

Integrin-mediated long-term B cell retention in the splenic marginal zone. (24/214)

The mechanisms that control localization of marginal zone (MZ) B cells are poorly understood. Here we show that MZ B cells express elevated levels of the integrins LFA-1 (alphaLbeta2) and alpha4beta1 and that they bind to the ligands ICAM-1 and VCAM-1. These ligands are expressed within the MZ in a lymphotoxin-dependent manner. Combined inhibition of LFA-1 and alpha4beta1 causes a rapid and selective release of B cells from the MZ. Furthermore, lipopolysaccharide-triggered MZ B cell relocalization involves down-regulation of integrin-mediated adhesion. These studies identify key requirements for MZ B cell localization and establish a role for integrins in peripheral lymphoid tissue compartmentalization.  (+info)