Vasoactive intestinal peptide promotes host defense against enteric pathogens by modulating the recruitment of group 3 innate lymphoid cells.

Group 3 innate lymphoid cells (ILC3s) control the formation of intestinal lymphoid tissues and play key roles in intestinal defense. They express neuropeptide vasoactive intestinal peptide (VIP) receptor 2 (VPAC2), through which VIP modulates their function, but whether VIP exerts other effects on ILC3 remains unclear. We show that VIP promotes ILC3 recruitment to the intestine through VPAC1 independent of the microbiota or adaptive immunity. VIP is also required for postnatal formation of lymphoid tissues as well as the maintenance of local populations of retinoic acid (RA)-producing dendritic cells, with RA up-regulating gut-homing receptor CCR9 expression by ILC3s. Correspondingly, mice deficient in VIP or VPAC1 suffer a paucity of intestinal ILC3s along with impaired production of the cytokine IL-22, rendering them highly susceptible to the enteric pathogen Citrobacter rodentium This heightened susceptibility to C. rodentium infection was ameliorated by RA supplementation, adoptive transfer of ILC3s, or by recombinant IL-22. Thus, VIP regulates the recruitment of intestinal ILC3s and formation of postnatal intestinal lymphoid tissues, offering protection against enteric pathogens.

The origin of prostate gland-secreted IgA and IgG.

The prostate secretes immunoglobulin (Ig) A (IgA) and IgG; however, how immunoglobulins reach the secretion, where the plasma cells are located, whether immunoglobulins are antigen-specific and where activation of the adaptive response occurs are still unknown. Immune cells, including CD45RA+ cells, were scattered in the stroma and not organized mucosae-associated lymphoid-tissue. IgA (but not IgG) immunostaining identified stromal plasma cells and epithelial cells in non-immunized rats. Injected tetramethylrhodamine-IgA transcytosed the epithelium along with polymeric immunoglobulin receptor. Oral immunization with ovalbumin/mesopourous SBA-15 silica adjuvant resulted in more stromal CD45RA+/IgA+ cells, increased content of ovalbumin-specific IgA and IgG, and the appearance of intraepithelial CD45RA+/IgG+ cells. An increased number of dendritic cells that cooperate in other sites with transient immunocompetent lymphocytes, and the higher levels of interleukin-1ß, interferon-γ and transforming growth factor-ß, explain the levels of specific antibodies. Nasal immunization produced similar results except for the increase in dendritic cells. This immunomodulatory strategy seems useful to boost immunity against genitourinary infections and, perhaps, cancer.

Cranberry proanthocyanidins improve intestinal sIgA during elemental enteral nutrition.

BACKGROUND: Elemental enteral nutrition (EEN) decreases gut-associated lymphoid tissue (GALT) function, including fewer Peyer's patch lymphocytes and lower levels of the tissue T helper 2 (Th2) cytokines and mucosal transport protein polymeric immunoglobulin receptor (pIgR), leading to lower luminal secretory immunoglobulin A (sIgA) levels. Since we recently demonstrated that cranberry proanthocyanidins (PACs) maintain the Th2 cytokine interleukin (IL)-4 when added to EEN, we hypothesized the addition of PACs to EEN would normalize other GALT parameters and maintain luminal levels of sIgA. METHODS: Institute of Cancer Research mice were randomized (12/group) to receive chow, EEN, or EEN + PACs (100 mg/kg body weight) for 5 days, starting 2 days after intragastric cannulation. Ileum tissue was collected to measure IL-4 by enzyme-linked immunosorbent assay, pIgR by Western blot, and phosphorylated STAT-6 by microarray. Intestinal wash fluid was collected to measure sIgA by Western blot. RESULTS: Compared with chow, EEN significantly decreased tissue IL-4, phosphorylated STAT-6, and pIgR. The addition of PACs to EEN prevented these alterations. Compared with chow, EEN resulted in significantly lower levels of luminal sIgA. The addition of PACs to EEN increased luminal sIgA levels compared with EEN alone. CONCLUSIONS: This study suggests the addition of PACs to EEN may support GALT function and maintain intestinal sIgA levels compared with EEN administration alone.

Enhanced intestinal epithelial barrier health status on European sea bass (Dicentrarchus labrax) fed mannan oligosaccharides.

The study assesses the effects of dietary mannan oligosaccharides (MOS) in European sea bass (Dicentrarchus labrax) posterior intestinal lipid class composition and its possible relation to the potential prostaglandins production and Gut Associated Lymphoid Tissue (GALT) stimulation. Fish were fed 4 g kg(-1) MOS (Bio-Mos(®) Aquagrade, Alltech, Inc., USA) for eight weeks. Fish fed MOS presented higher (P ≤ 0.05) weight gain, total length, and specific and relative growth rates than fish fed the control diet. Stimulated posterior gut of fish fed MOS showed higher (P ≤ 0.05) prostaglandins production than fish fed the control diet. Lipid class analyses of posterior gut revealed a reduction (P ≤ 0.05) in the neutral lipid fraction in fish fed MOS compared to fish fed the control diet, particularly due to a reduction (P ≤ 0.05) in triacylglycerols content. The polar lipid fraction increased (P ≤ 0.05) in fish fed MOS compared to fish fed the control diet, mainly due to an increase (P ≤ 0.05) in phosphatidylethanolamine and phosphatidylcoline contents. Light microscopy of posterior gut revealed increased number or goblet cells as well as higher level of infiltrated eosinophilic granulocytes for fish fed MOS. Transmission electron microscopy qualitative observations revealed a better preserved cytoarchitecture of the intestinal epithelial barrier in the posterior gut of fish fed MOS. Posterior gut of fish fed MOS presented more densely packed non-damaged enterocytes, better preserved tight junctions structure, healthier and more organized microvilli, and a higher presence of infiltrated lymphocytes and granulocytes compared fish fed the control diet. The present study indicates that dietary MOS enhances European sea bass posterior gut epithelial defense by increasing membrane polar lipids content in relation to a stimulation of the eicosanoid cascade and GALT, promoting posterior gut health status.

Melatonin ameliorates oxidative stress and induces cellular proliferation of lymphoid tissues of a tropical rodent, Funambulus pennanti, during reproductively active phase.

Effect of melatonin treatment on free radical production was assessed with simultaneous investigation of hormonal level (melatonin and testosterone), blastogenic response, stimulation index, and histological observation of lymphoid organs (spleen, thymus, and bone marrow) in male Indian palm squirrel (Funambulus pennanti) during reproductively active phase (RAP). Low endogenous melatonin and high testosterone level were noted during RAP. Daily subcutaneous injection of melatonin (25 µg/100 g B wt.) at 17.30-18.00 h to squirrels for 60 consecutive days during May-June significantly decreased the thiobarbituric acid reactive substances (TBARS) level compared to control squirrels. Melatonin treatment significantly increased % stimulation ratio (%SR) of splenocytes and thymocytes against T cell mitogen concanavalin A. Pinealectomy (Px) led to a significant increase in TBARS level whereas a significant decrease was observed in blastogenic response and stimulation index was noted. Melatonin injection to Px squirrels showed restoration in %SR of thymocytes and splenocytes with a significant decrease in the TBARS level of the lymphoid tissues. Further, free radical load was induced by lipopolysaccharide (LPS; 400 µg/ml) in lymphatic tissue homogenates and noted that melatonin supplementation (2 mM/ml) led to a significant decrease in TBARS level compared to the control and LPS-supplemented groups. Histological observation showed dense cellularity of thymocytes and splenocytes. Acridine orange staining technique shows a significant increase in thymocyte apoptosis Px squirrels when compared with melatonin-treated squirrels. These findings suggest that endogenous and exogenous melatonin might be responsible for the maintenance of immune system to adapt this seasonal breeder for the rigors of the environmental changes.

Colon irrigation causes lymphocyte movement from gut-associated lymphatic tissues to peripheral blood.

It is well established that the intestine is an important site responsible for the local immune system. It is speculated that people suffering from constipation and carrying fecal residues in the intestine may have a decreased function of this immune system. In this study, colon irrigation, which is cleansing of the colon using a simple hydrotherapy instrument, was performed in 10 subjects with or without the disease. The number of leukocytes and their demarcation were then evaluated. The number and ratio of lymphocytes increased significantly after irrigation. This result suggested that colon irrigation might induce lymphocyte transmigration from gut-associated lymphatic tissues into the circulation, which may improve colon and immune system function.

TLR-induced local metabolism of vitamin D3 plays an important role in the diversification of adaptive immune responses.

The addition of monophosphoryl lipid A, a minimally toxic derivative of LPS, to nonmucosally administered vaccines induced both systemic and mucosal immune responses to coadministered Ags. This was dependent on an up-regulated expression of 1alpha-hydroxylase (CYP27B1, 1alphaOHase), the enzyme that converts 25-hydroxycholecalciferol, a circulating inactive metabolite of vitamin D(3), into 1,25(OH)2D(3) (calcitriol). In response to locally produced calcitriol, myeloid dendritic cells (DCs) migrated from cutaneous vaccination sites into multiple secondary lymphoid organs, including classical inductive sites of mucosal immunity, where they effectively stimulated B and T cell immune responses. The endogenous production of calcitriol by monophosphoryl lipid A-stimulated DCs appeared to be Toll-IL-1R domain-containing adapter-inducing IFN-beta-dependent, mediated through a type 1 IFN-induced expression of 1alphaOHase. Responsiveness to calcitriol was essential to promote the trafficking of mobilized DCs to nondraining lymphoid organs. Collectively, these studies help to expand our understanding of the physiologically important roles played by locally metabolized vitamin D(3) in the initiation and diversification of adaptive immune responses. The influences of locally produced calcitriol on the migration of activated DCs from sites of vaccination/infection into both draining and nondraining lymphoid organs create a condition whereby Ag-responsive B and T cells residing in multiple lymphoid organs are able to simultaneously engage in the induction of adaptive immune responses to peripherally administered Ags as if they were responding to an infection of peripheral or mucosal tissues they were designed to protect.

The effect of selenium and vitamin E on the lymphocytes and immunoglobulin-containing plasma cells in the lymphoid organ and mucosa-associated lymphatic tissues of broiler chickens.

The present research has been designed to understand the effect of selenium and vitamin E on the lymphocyte and changes in the frequency of Ig-containing plasma cells in the lymphatic organ and ileum (representative organ for mucosa-associated lymphatic tissues) of different postnatal stages of Kasilla broiler chickens. A routine haematoxylin and eosin (H and E) stain were used to study the histology of the lymphocytic changes, and indirect immunoperoxidase staining method was performed for the study of the distributional and dynamical changes of the Ig-containing plasma cells within the lymphatic tissues and in the ileum of control broilers and in the broilers supplemented with different concentration of selenium and vitamin E in the diet. Histologically, the population of lymphocytes decreased in the lobules of the thymus, medulla of bursal follicles, splenic masses, lymphatic nodules of the cecal tonsil, and villi of the ilium in 0.1 mg and 0.5 mg selenium supplemented broilers in comparison with the control. The population of these cells was found to increase in 150 mg and 300 mg vitamin E supplemented chickens in the present study. In the spleen IgG- and the IgM-containing plasma cells were more than IgA-containing plasma cells. In contrast, in the cecal tonsil and ileum IgA-containing plasma cells were more than IgG- and IgM-containing plasma cells. The frequency of these immunopositive cells were decreased in 0.1 mg and 0.5 mg selenium supplementated chickens, and increased their frequency in the chickens supplemented with 150 mg and 300 mg vitamin E. In the spleen the frequency of IgM-containing plasma cells and both in the cecal tonsil and ileum, the IgG-containing plasma cells were more decreased by selenium supplementation which restored in their population by vitamin E supplementation.

Population of CD40L-expressing cells was slightly but not significantly decreased in lymphoid tissues of collagen-induced arthritic mice treated with Hochu-Ekki-To.

OBJECTIVE: To clarify the mechanism of the action of Hochu-Ekki-To (HET) on collagen-induced arthritic (CIA) mice by analyzing the CD40L-expressing cells population. METHODS: CIA was induced in male DBA/1J mice by immunization with two injections of bovine type II collagen (CII). HET or water was orally administered. The subpopulations of lymphocytes obtained from lymph nodes and spleen were detected at 3 weeks after boost using flow cytometry. RESULTS: Although the population of CD4+CD40L+ cells tended to be decreased in the HET group compared to that in control mice, there was no significant difference between the two groups. These findings were observed in lymphocytes obtained from both lymph nodes and spleen. CONCLUSION: HET suppresses the development of CIA. These effects may be partially induced via the decrease in the population of CD4+CD40L+ cells, but the role of this action is probably limited.

Expression of mitochondria-related genes in lymphoblastoid cells from patients with bipolar disorder.

OBJECTIVES: Several studies have suggested mitochondrial abnormality in bipolar disorder. We reported the association of mitochondrial complex I subunit gene, NDUFV2 at 18p11, with bipolar disorder. A decrease in the mRNA expression of this gene was found in patients with bipolar disorder compared with controls. However, it was unclear whether only the NDUFV2 gene exhibited the decreased expression level in bipolar disorder. The aim of this study was to clarify the association of other nuclear-encoded complex I subunit genes and mitochondria-related genes with bipolar disorder. METHODS: We quantified the mRNA expression level of five nuclear-encoded mitochondrial complex I subunit genes located at the chromosomal regions linked with bipolar disorder other than NDUFV2, three complex IV subunit genes, and four mitochondrial transcription-related genes using a real-time quantitative reverse transcription polymerase chain reaction method in the lymphoblastoid cell lines from 21 patients with bipolar disorder and 11 controls. RESULTS: Decreased mRNA expression in patients with bipolar I disorder compared with control subjects was found in most of the complex I subunit genes. In addition, decreased expression levels of these genes correlated with that of NDUFV2. No statistically significant alterations of mRNA expression levels were found between bipolar patients and controls among two of three complex IV subunit genes and all transcription-related genes. CONCLUSIONS: Our study suggests that the decreased expression of NDUFV2 has a considerable effect on other subunit genes in the mitochondrial respiratory chain and presents further evidence of the biological significance of NDUFV2 in bipolar disorder.

Oral administration of bovine colostrum stimulates intestinal intraepithelial lymphocytes to polarize Th1-type in mice.

Th1 stimulus for Th2-skewed immune response during infancy is important for reduction of incidence of allergic diseases. We examined effects of oral administration of bovine colostrum on local immunity in intestine in adult mice. C57BL/6 mice were orally given bovine colostrum or control milk for 1, 3 or 6 months and intestinal microflora, fecal IgA, and lymphocyte population of gut-associated lymphoid tissues and their abilities of cytokine production were examined. Although the cell populations of intestinal intraepithelial lymphocytes (i-IEL) were not remarkably changed, the T cells in i-IEL were polarized to Th1 type after oral administration of bovine colostrum. Intestinal microflora and IgA levels in feces were not changed by oral administration of bovine colostrum. These results suggest that colostrum stimulates directly to i-IEL to polarize Th1 type, which may protect from infectious diseases and allergic diseases mediated by Th2 type responses.

[Correction of immune and hematopoietic system disorders in experimental toxic hepatitis with Lacto Flor]. / Korrektsiia narushenii v immunoi i krovetvornoi sistemakh pri toksicheskom gepatite s pomoshch'iu Lacto Flor v éksperimente.

Reduction in cells quantity of thymus, lymphatic nodes, bone marrow and rosette formation cells, decrease in erythrocytes and leucocytes number, suppression of antibody production are seen in experimentally developed acute toxic hepatitis (ATH). Lacto Flor preparation was established to have potential properties to restore different immune and hematological systems disorders observed in mice with ATH.

L-arginine-enriched parenteral nutrition affects lymphocyte phenotypes of gut-associated lymphoid tissue.

BACKGROUND: Experimentally, total parenteral nutrition (TPN) diminishes gut-associated lymphoid tissue (GALT) cell numbers and function. Although glutamine supplementation is known to reverse TPN-induced changes in GALT, effects of another conditionally essential amino acid, L-arginine (ARG), on GALT remain unclear. METHODS: Twenty-two male Institute of Cancer Research mice were randomized to standard TPN (0.3% arginine, STD-total parenteral nutrition) or 1% ARG-enriched TPN (ARG-total parenteral nutrition). After 5 days of feeding, lymphocytes were harvested from Peyer's patches (PP), the lamina propria, and intraepithelial (IE) spaces of the small intestine to determine cell yields. Lymphocyte phenotypes (alphabetaTCR, gammadeltaTCR, CD4, CD8, and B220 as a B cell marker) were determined using flow cytometry. IgA levels in washings of the small intestine, upper respiratory tract, and lungs were measured with ELISA. RESULTS: ARG-total parenteral nutrition did not affect lymphocyte yields. The percentages of CD4+ cells in PP and IE, and alphabetaTCR+ cells in PP, were significantly higher in the ARG-total parenteral nutrition than in the STD-total parenteral nutrition mice, without marked differences in other phenotypes examined. There were no significant differences in intestinal and respiratory tract IgA levels between the 2 groups of mice. CONCLUSIONS: One percent ARG supplementation of TPN does not improve GALT cell number or mucosal IgA level but benefits to increase CD4+ cell percentages in GALT.

The Gads (GrpL) adaptor protein regulates T cell homeostasis.

Little is known about the role of the Gads (GrpL) adaptor protein in mature T cell populations. In this study we show that the effects of Gads deficiency on murine CD4(+) and CD8(+) T cells are markedly different. Gads(-/-) CD4(+) T cells were markedly deficient in the spleen and had an activated phenotype and a rapid turnover rate. When transferred into a wild-type host, Gads(-/-) CD4(+) T cells continued to proliferate at a higher rate than wild-type CD4(+) T cells, demonstrating a defect in homeostatic proliferation. Gads(-/-) CD8(+) T cells had a memory-like phenotype, produced IFN-gamma in response to ex vivo stimulation, and underwent normal homeostatic proliferation in wild-type hosts. Gads(-/-) T cells had defective TCR-mediated calcium responses, but had normal activation of ERK. Gads(-/-) CD4(+) T cells, but not CD8(+) T cells, had a severe block of TCR-mediated proliferation and a high rate of spontaneous cell death and were highly susceptible to CD95-induced apoptosis. This suggests that the rapid turnover of Gads(-/-) CD4(+) T cells is due to a defect in cell survival. The intracellular signaling pathways that regulate homeostasis in CD4(+) and CD8(+) T cells are clearly different, and the Gads adaptor protein is critical for homeostasis of CD4(+) T cells.

[The influence of the dietary polyunsaturated fatty acids on the phagocyte's functional activity in rats]. / Vliianie polinenasyshchennykh zhirnykh kislot ratsiona na funktsional'nuiu aktivnost' fagotsitov u krys.

The influence of dietary polyunsaturated fatty acids on the superoxid anion production by peritoneal macrophages and phagocytosis by blood neutrophiles in male Wistar rats weighting 127.0 +/- 3.2 r was investigated after 3 months feeding. Rats fed isocaloric purified diets contained 24% fat representing combinations of lard, sunflower oil and fish oil (eiconol) providing the ratios of w6/w3 fatty acids equal 49.0; 6.1; 1.1. The increasing of superoxide formed by peritoneal macrophages and phagocytic activity of neutrophiles in the group received diet with the minimal ratios of w6/w3 fatty acids compared to that in rats fed diet with ratio 49.0 was noted. The increased activity of mononuclear-phagocytic system was confirmed by morphological investigation of peripheral lymphoid organs.

Identification of mouse langerin/CD207 in Langerhans cells and some dendritic cells of lymphoid tissues.

Human (h)Langerin/CD207 is a C-type lectin of Langerhans cells (LC) that induces the formation of Birbeck granules (BG). In this study, we have cloned a cDNA-encoding mouse (m)Langerin. The predicted protein is 66% homologous to hLangerin with conservation of its particular features. The organization of human and mouse Langerin genes are similar, consisting of six exons, three of which encode the carbohydrate recognition domain. The mLangerin gene maps to chromosome 6D, syntenic to the human gene on chromosome 2p13. mLangerin protein, detected by a mAb as a 48-kDa species, is abundant in epidermal LC in situ and is down-regulated upon culture. A subset of cells also expresses mLangerin in bone marrow cultures supplemented with TGF-beta. Notably, dendritic cells in thymic medulla are mLangerin-positive. By contrast, only scattered cells express mLangerin in lymph nodes and spleen. mLangerin mRNA is also detected in some nonlymphoid tissues (e.g., lung, liver, and heart). Similarly to hLangerin, a network of BG form upon transfection of mLangerin cDNA into fibroblasts. Interestingly, substitution of a conserved residue (Phe(244) to Leu) within the carbohydrate recognition domain transforms the BG in transfectant cells into structures resembling cored tubules, previously described in mouse LC. Our findings should facilitate further characterization of mouse LC, and provide insight into a plasticity of dendritic cell organelles which may have important functional consequences.

Orally administered Kampo (Japanese herbal) medicine, "Juzen-Taiho-To" modulates cytokine secretion in gut associated lymphoreticular tissues in mice.

The influence of the oral administration of Juzen-Taiho-To (JTT; Si-Quan-Da-Bu-Tang in Chinese), a Kampo (Japanese herbal) medicine, on the cytokine production in mice were investigated. Lymphocytes from spleen (SPN), mesenteric lymph node (MLN) and Peyer's patches (PP) from mice, which received orally administered JTT for 2 weeks, were stimulated with concanavalin A (Con A), and the resulting conditioned medium was tested for cytokine production by ELISA. Administration of JTT caused enhancement of interferon g (IFN-gamma) and interleukin-4 (IL-4) production to some extent but decreased IL-5 production from the SPN. On the other hand, notable changes in cytokine production were observed in lymphocytes from MLN and PP. Administration of JTT increased IFN-gamma production remarkably, as well as IL-5 secretion from both MLN and PP, whereas IL-2 secretion was plainly reduced. The ratio of IFN-gamma and IL-4 was shifted to Th1 dominant in MLN and PP, however changed little in SPN. The flow cytometric analysis revealed that the population of CD3+, CD4+, CD45R/B220+, and CD45RBlowCD4+ cells in each lymphocyte was not changed significantly after oral administration of JTT. These findings demonstrate that the lymphocytes from gut associated lymphoreticular tissues (GALT) are more sensitive to produce cytokines on cytokine production than those from SPN by oral administration of JTT, and that the modulation of cytokine production may be due to functional change of lymphocytes but not change in lymphocytes population.

Immunomodulatory activity of a Unani gold preparation used in Indian system of medicine.

Kushta Tila Kalan (KTK), a gold preparation used in Unani-Tibb is claimed to possess general tonic, anti-infective and rejuvenating properties. We evaluated immunomodulatory activity of KTK in male mice. KTK was orally administered to animals at dosage of 6.25, 12.5, 25 and 50 mg/kg b.w. for 10 days. Beside general immunopathological parameters, cell-mediated immunity was evaluated by measuring delayed type of hypersensitivity response (DTH) while humoral immunity was assessed using plaque forming cell (PFC) assay. KTK augmented both the immune responses at dose levels of 6.25, 12.5 and 25 mg/kg. The optimum activities were recorded at 25 mg/kg. High dose of 50 mg/kg showed suppressive effects on immune functions. The modulatory effects may be attributed to the interactions of gold with herbomineral adjuncts incorporated during the specialized ashing techniques used in the preparation. The results are interesting in view of reported suppressive effects of other gold preparations.

Splenic adherent cells, stimulated in vitro, induce the reactive formation of lymphoid follicles and germinal centres in draining lymph nodes after subcutaneous transfusion into syngeneic mice.

The reactive formation of lymphoid follicles and germinal centres in lymph nodes, induced by subcutaneous transfer of in vitro activated splenic adherent cells into syngeneic mice, were studied. Adherent cells were obtained by incubating spleen cell suspensions for 24 h and activated by incubating for 1 h in the medium containing keyhole limpet haemocyanin (KLH) absorbed onto alumina. Some of the treated adherent cells were irradiated with 10 Gy x-rays, while others were either not stimulated or were stimulated with alumina-KLH but killed by repeated freezing and thawing. Examination of adherent cell smears immunostained with antibodies against, F4/80, Mac-1, Mac-2 and NLDC-145 indicated that many adherent cells displayed macrophage markers but few displayed the interdigitating cell marker. Animals transfused with KLH-treated adherent cells with or without irradiation showed a marked increase in the number of lymphoid follicles and germinal centres in draining lymph nodes, whereas those transfused with adherent cells which had not been KLH-treated or which had been killed after KLH treatment displayed no significant change in the number of follicles. These results were interpreted as indicating that following transfusion, antigen-activated adherent macrophages migrated into the draining lymph nodes and induced the reactive formation of lymphoid follicles and germinal centres outside preexisting follicles.

A B-cell-homing chemokine made in lymphoid follicles activates Burkitt's lymphoma receptor-1.

Secondary lymphoid organs (spleen, lymph nodes and Peyer's patches) are divided into compartments, such as B-cell zones (follicles) and T-cell zones, which provide specialized environments for specific steps of the immune response. Migration of lymphocyte subsets into these compartments is essential for normal immune function, yet the molecular cues guiding this cellular traffic are poorly defined. Chemokines constitute a family of chemotactic cytokines that have been shown to direct the migration of leukocytes during inflammation and which may be involved in the constitutive homing of lymphocytes into follicles and T-cell zones. Here we describe a novel chemokine, B-lymphocyte chemoattractant (BLC), that is strongly expressed in the follicles of Peyer's patches, the spleen and lymph nodes. BLC strongly attracts B lymphocytes while promoting migration of only small numbers of T cells and macrophages, and therefore is the first chemokine to be identified that is selective towards B cells. An orphan chemokine receptor, Burkitt's lymphoma receptor 1 (BLR-1), has been found to be required for B-cell migration into lymphoid follicles. We show that BLC stimulates calcium influx into, and chemotaxis of, cells transfected with BLR-1. Our results indicate that BLC functions as a BLR-1 ligand and may guide B lymphocytes to follicles in secondary lymphoid organs.