Sphingosine 1-phosphate regulates peritoneal B-cell trafficking for subsequent intestinal IgA production

Blood ◽  
2007 ◽  
Vol 109 (9) ◽  
pp. 3749-3756 ◽  
Author(s):  
Jun Kunisawa ◽  
Yosuke Kurashima ◽  
Masashi Gohda ◽  
Morio Higuchi ◽  
Izumi Ishikawa ◽  
...  
Keyword(s):  
B Cells ◽  
Lymph Nodes ◽  
B Cell ◽  
Antibody Production ◽  
Pivotal Role ◽  
Secretory Iga ◽  
Lymphoid Tissues ◽  
Sphingosine 1 Phosphate ◽  
S1p Receptor ◽  
Iga Production

AbstractSphingosine 1-phosphate (S1P) is known to play a pivotal role in the regulation of lymphocyte emigration from organized lymphoid tissues such as the peripheral lymph nodes and thymus, but its immunologic role in unorganized and diffused tissues remains to be elucidated. Here we show that the trafficking of peritoneal B cells is principally regulated by S1P. All peritoneal B cells including B1a, B1b, and B2 B cells express comparable levels of the type 1 S1P receptor. Thus, treatment with FTY720, an S1P receptor modulator, caused the rapid disappearance of peritoneal B cells by inhibiting both their emigration from parathymic lymph nodes and their recirculation from the blood into the peritoneal cavity without affecting their progenitor populations. These changes did not affect natural plasma antibody production or phosphorylcholine (PC)–specific antibody production in serum after peritoneal immunization with heat-killed Streptococcal pneumoniae (R36A). However, FTY720 dramatically reduced peritoneal B cell-derived natural intestinal secretory IgA production without affecting the expression of J-chain and polyimmunoglobulin receptors. Additionally, FTY720 impaired the generation of PC-specific fecal IgA responses after oral immunization with R36A. These findings point to a pivotal role for S1P in connecting peritoneal B cells with intestinal B-cell immunity.

scholarly journals Rituximab efficiently depletes B cells in lung tumors and normal lung tissue

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 38 ◽  
Author(s):  
Albane Joly-Battaglini ◽  
Clara Hammarström ◽  
Branislava Stankovic ◽  
Henrik Aamodt ◽  
Johan Stjärne ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
B Cells ◽  
Lymph Nodes ◽  
B Cell ◽  
Lung Tissue ◽  
Lung Tumor ◽  
B Cell Lymphoma ◽  
Normal Lung Tissue ◽  
Normal Lung ◽  
Lymphoid Tissues

Rituximab is a monoclonal antibody that targets the CD20 B-cell-specific antigen and is widely used as therapy for B-cell lymphoma. Since rituximab depletes both malignant and normal B cells, it is increasingly being used to treat various conditions in which normal B cells have a pathogenic role, such as rheumatoid arthritis and multiple sclerosis. It is well-established that rituximab efficiently eliminates B cells in blood, lymph nodes, and spleen. In contrast, the effect of rituximab in non-lymphoid tissues remains poorly documented and is debated. Here, we report a rheumatoid arthritis patient who was treated with rituximab before receiving thoracic surgery for non-small cell lung cancer. Using flow cytometry and immunohistochemistry, we show that rituximab efficiently depleted CD20-positive B cells in a primary lung tumor, in lung-associated lymph nodes, and in normal lung tissue. We conclude that rituximab may be very efficient at depleting normal B cells in the lungs. This property of rituximab may potentially be exploited for the treatment of conditions in which pathogenic B cells reside in the lungs. On the other hand, the clearance of lung B cells may provide an explanation for the rare cases of severe non-infectious pulmonary toxicity of rituximab.

microRNA-21 Is Differentially Expressed in the Lymphoid Tissue and Modulated By Stromal Signaling in Chronic Lymphocytic Leukemia

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1975-1975
Author(s):  
Cody Paiva ◽  
Olga Danilova ◽  
Ahsan S Kamal ◽  
Prabhjot Kaur ◽  
Alexey V. Danilov
Keyword(s):  
B Cells ◽  
Lymph Nodes ◽  
B Cell ◽  
Peripheral Blood ◽  
Lymphoid Tissue ◽  
Differentially Expressed ◽  
Lymphoid Tissues ◽  
Mutational Status ◽  
Bcr Signaling

Abstract MicroRNAs contribute to the initiation and dissemination of malignant clone and serve as important prognostic indicators. miR-21 overexpression was linked to fludarabine resistance and unfavorable prognosis in CLL. We and others have shown that B-cell receptor (BCR) signaling upregulates miR-21 in CLL. While recent literature addresses the impact of miR-21 in the circulating malignant B cells, few studies have focused on its expression in CLL lymph nodes, where cells receive stromal pro-survival signals including via BCR. In those tissues, some microRNAs demonstrate distinct expression patterns, e.g. miR-155 is highly expressed in the proliferation centers. Here we aimed to investigate miR-21 expression in the lymphoid tissue and assessed the effect of the modeled lymphoid niche on this MIR in CLL cells in vitro. Expression of miR-21, RNU6B and CD20 was assessed in 30 formalin fixed paraffin-embedded lymph nodes from patients with CLL and 4 control (tonsil) tissues using a modified combined FISH/IHC assay. miR-21 was differentially expressed in the lymphoid tissues of patients with CLL: miR-21 was detected in 13/30 lymph nodes (43%), with three demonstrating strong and ten - weak staining. The remaining 17 tissue specimens (56%) stained negative for miR-21. Where present, strong miR-21 expression followed focal rather than diffuse staining pattern. Foci of miR-21 did not localize to the proliferation centers as per morphologic assessment. Since microRNAs are also expressed in other cell types including stromal cells, we used CD20 to confirm that miR-21 expression was detected in the neoplastic CLL cells. miR-21 positivity in the lymphoid tissue did not predict time to first treatment or correlate with either CD38 or ZAP-70 expression. Interestingly, 2/4 control tissues demonstrated strong staining for MIR21, indicating that its expression in the lymphoid organs is not restricted to clonal neoplastic B-cells. We further studied whether miR-21 expression was modulated by stromal signaling. Peripheral blood CLL cells (n=33) and normal B-cells (n=7) were isolated using standard Ficoll-Hypaque techniques, B-cell isolation kit and CD19 MACS microbeads, followed by cDNA synthesis and RT-PCR with specific TaqMan probes. We modeled lymph node microenvironment in vitro using CD40L-expressing or control mouse L cells, thus promoting drug resistance and survival of the peripheral blood CLL; CD40L-expressing cells induced NFκB. Consistent with previous reports, we found increased levels of miR-21 in peripheral blood CLL cells compared with normal B-cells. Co-culture of CLL cells with stroma resulted in induction of miR-21. IGHV mutational status is closely associated with BCR signaling capacity in CLL and predicts cellular reliance on microenvironmental support. We did not find a correlation between baseline miR-21 expression and IGHV mutational status in circulating CLL cells. However, CLL cells with unmutated IGHV were stronger inducers of miR-21 in response to stromal signaling. Meanwhile, CD40L-expressing stroma led to further induction of miR-155, a recognized NFκB target, but not miR-21, indicating that alternative mechanisms are responsible for stromal modulation of this microRNA. In summary, here for the first time we successfully visualized miR-21 expression within the neoplastic B-cells in the lymphoid tissues from patients with CLL. miR-21 was induced in stromal CLL cell co-cultures, primarily in cells with unmutated IGHV. Our observations are particularly relevant in the current era where BCR signaling pathways have become key pharmacologic targets. These therapies disrupt CLL–stroma interactions leading to an egress of CLL cells to the periphery, where they are unable to proliferate. Analysis of expression of miR-21 in lymph nodes and peripheral blood of patients treated with the BCR-targeting agents may clarify its predictive role in this setting as well as shed additional light on the mechanisms involved in its regulation. Disclosures No relevant conflicts of interest to declare.

scholarly journals Induction of Mucosal B-Cell Memory by Intranasal Immunization of Mice with Respiratory Syncytial Virus

2005 ◽  
Vol 12 (1) ◽  
pp. 171-179 ◽  
Author(s):  
Janine Valosky ◽  
Haruka Hishiki ◽  
Theoklis E. Zaoutis ◽  
Susan E. Coffin
Keyword(s):  
Respiratory Syncytial Virus ◽  
B Cells ◽  
Lymph Nodes ◽  
B Cell ◽  
Memory B Cells ◽  
Lymphoid Tissues ◽  
Primary Immunization ◽  
Cell Memory ◽  
B Cell Memory ◽  
Syncytial Virus

ABSTRACT The capacity of live or inactivated respiratory syncytial virus (RSV) to induce B-cell memory in respiratory-associated lymphoid tissues of mice was examined. Eight weeks after primary inoculation with either live or inactivated RSV, adult BALB/c mice were challenged with 4 × 105 PFU of RSV. Protection from viral shedding and mucosal production of RSV-specific antibodies were examined at various time points after challenge. We found that primary immunization with live, but not inactivated, RSV induced complete and durable protection upon challenge within the upper and lower respiratory tract. Also, primary immunization with live, but not inactivated, RSV enhanced the production of mucosal RSV-specific immunoglobulin A (IgA) upon challenge. Secondary mucosal IgA responses were characterized by (i) the early production of mucosal IgA by B cells that reside in organized nasal-associated lymphoid tissues, cervical lymph nodes, and bronchial lymph nodes, and (ii) the subsequent production of RSV-specific IgA by mucosal effector tissues, such as the tracheal lamina propria and lung. These findings suggest that primary infection of mice with live RSV might induce mucosal IgA-committed memory B cells. A greater understanding of the characteristics of RSA-specific mucosal memory B cells may facilitate the development of an RSV vaccine.

Expression of the IRTA1 receptor identifies intraepithelial and subepithelial marginal zone B cells of the mucosa-associated lymphoid tissue (MALT)

Blood ◽  
2003 ◽  
Vol 102 (10) ◽  
pp. 3684-3692 ◽  
Author(s):  
Brunangelo Falini ◽  
Enrico Tiacci ◽  
Alessandra Pucciarini ◽  
Barbara Bigerna ◽  
Julia Kurth ◽  
...  
Keyword(s):  
B Cells ◽  
Lymph Nodes ◽  
B Cell ◽  
Cell Population ◽  
Lymphoid Tissue ◽  
Marginal Zone ◽  
Plasma Cells ◽  
Immunoglobulin Superfamily ◽  
Lymphoid Tissues ◽  
Marginal Zone B Cells

AbstractIRTA1 (immunoglobulin superfamily receptor translocation-associated 1) is a novel surface B-cell receptor related to Fc receptors, inhibitory receptor superfamily (IRS), and cell adhesion molecule (CAM) family members and we mapped for the first time its distribution in human lymphoid tissues, using newly generated specific antibodies. IRTA1 was selectively and consistently expressed by a B-cell population located underneath and within the tonsil epithelium and dome epithelium of Peyer patches (regarded as the anatomic equivalents of marginal zone). Similarly, in mucosa-associated lymphoid tissue (MALT) lymphomas IRTA1 was mainly expressed by tumor cells involved in lympho-epithelial lesions. In contrast, no or a low number of IRTA1+ cells was usually observed in the marginal zone of mesenteric lymph nodes and spleen. Interestingly, monocytoid B cells in reactive lymph nodes were strongly IRTA1+. Tonsil IRTA1+ cells expressed the memory B-cell marker CD27 but not mantle cell-, germinal center-, and plasma cell-associated molecules. Polymerase chain reaction (PCR) analysis of single tonsil IRTA1+ cells showed they represent a mixed B-cell population carrying mostly mutated, but also unmutated, IgV genes. The immunohistochemical finding in the tonsil epithelial areas of aggregates of IRTA1+ B cells closely adjacent to plasma cells surrounding small vessels suggests antigen-triggered in situ proliferation/differentiation of memory IRTA1+ cells into plasma cells. Collectively, these results suggest a role of IRTA1 in the immune function of B cells within epithelia. (Blood. 2003;102: 3684-3692)

Sphingosine 1-phosphate–dependent trafficking of peritoneal B cells requires functional NFκB-inducing kinase in stromal cells

Blood ◽  
2008 ◽  
Vol 111 (9) ◽  
pp. 4646-4652 ◽  
Author(s):  
Jun Kunisawa ◽  
Masashi Gohda ◽  
Yosuke Kurashima ◽  
Izumi Ishikawa ◽  
Morio Higuchi ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Stromal Cells ◽  
Nuclear Factor Κb ◽  
Cell Trafficking ◽  
Wild Type ◽  
Sphingosine 1 Phosphate ◽  
Underlying Mechanisms ◽  
Iga Production

Abstract We previously reported that sphingosine 1-phosphate (S1P) regulates peritoneal B-cell trafficking and subsequent intestinal IgA production, but the underlying mechanisms remain obscure. We demonstrate here that nuclear factor κB–inducing kinase (NIK) is involved in the regulation of S1P-mediated trafficking of peritoneal B cells. Although peritoneal B cells from NIK-mutated alymphoplasia (aly) mice expressed type 1 S1P receptor (S1P1) at comparable levels and demonstrated normal migration toward S1P, aly peritoneal B cells showed decreased sensitivity to FTY720, an S1P1 modulator. NIK-mutated stromal cells showed decreased levels of adhesion molecules (VCAM-1 and ICAM-1) and increased CXCL13 expressions, leading to impaired ability to support S1P-mediated emigration, but not immigration, of peritoneal B cells. Therefore, aly peritoneal B cells exhibited normal S1P-mediated peritoneal B-cell trafficking from peritoneum to intestine for IgA production when they were transferred into severe combined immunodeficient or wild-type mice. However, S1P-mediated emigration of wild-type B cells from the aly peritoneal cavity was impaired without affecting their immigration from the blood. Further, transfer of wild-type stromal cells into the peritoneum restored S1P-mediated trafficking of aly peritoneal B cells. These findings suggest that NIK in stromal cells has a specific role in the regulation of S1P-mediated trafficking of peritoneal B cells.

scholarly journals Human Immunodeficiency Virus Type 1 Bound to B Cells: Relationship to Virus Replicating in CD4+ T Cells and Circulating in Plasma

2002 ◽  
Vol 76 (17) ◽  
pp. 8855-8863 ◽  
Author(s):  
Angela Malaspina ◽  
Susan Moir ◽  
David C. Nickle ◽  
Eileen T. Donoghue ◽  
Kisani M. Ogwaro ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
B Cells ◽  
Lymph Nodes ◽  
B Cell ◽  
Peripheral Blood ◽  
Lymphoid Tissues ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT Human immunodeficiency virus type 1 (HIV-1) virions bind to B cells in the peripheral blood and lymph nodes through interactions between CD21 on B cells and complement-complexed virions. B-cell-bound virions have been shown to be highly infectious, suggesting a unique mode of HIV-1 dissemination by B cells circulating between peripheral blood and lymphoid tissues. In order to investigate the relationship between B-cell-bound HIV-1 and viruses found in CD4+ T cells and in plasma, we examined the genetic relationships of HIV-1 found in the blood and lymph nodes of chronically infected patients with heteroduplex mobility and tracking assays and DNA sequence analysis. In samples from 13 of 15 patients examined, HIV-1 variants in peripheral blood-derived B cells were closely related to virus in CD4+ T cells and more divergent from virus in plasma. In samples from five chronically viremic patients for whom analyses were extended to include lymph node-derived HIV-1 isolates, B-cell-associated HIV-1 and CD4+-T-cell-associated HIV-1 in the lymph nodes were equivalent in their divergence from virus in peripheral blood-derived B cells and generally more distantly related to virus in peripheral blood-derived CD4+ T cells. These results indicates virologic cross talk between B cells and CD4+ T cells within the microenvironment of lymphoid tissues and, to a lesser extent, between cells in lymph nodes and the peripheral blood. These findings also indicate that most of the virus in plasma originates from cells other than CD4+ T cells in the peripheral blood and lymph nodes.

scholarly journals Mechanisms regulating IgA class-specific immunoglobulin production in murine gut-associated lymphoid tissues. II. Terminal differentiation of postswitch sIgA-bearing Peyer's patch B cells.

1983 ◽  
Vol 158 (3) ◽  
pp. 649-669 ◽  
Author(s):  
H Kawanishi ◽  
L Saltzman ◽  
W Strober
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
Present Report ◽  
Protein A ◽  
Cell Subset ◽  
Terminal Differentiation ◽  
Lymphoid Tissues ◽  
T Cell Subset ◽  
Iga Production

Our previous studies indicated that cloned T cells obtained from Peyer's patches (PP) (Lyt-1+, 2-, Ia+, and H-2K/D+) evoked immunoglobulin (Ig) class switching of PP B cells from sIgM to sIgA cells in vitro; however, these switch T cells could not in themselves provide optimal help for the differentiation of postswitch sIgA-bearing PP B cells to IgA-secreting cells. Thus, in the present report we described studies focused on mechanisms regulating terminal differentiation of the postswitch PP sIgA-bearing B cells. First, to explore the effect of T cell-derived B cell differentiation factor(s) (BCDF) and macrophage factor(s) (MF) on the terminal maturation of PP B cells, LPS-stimulated PP B cells were co-cultured for 7 d with cloned T cells in the presence or absence of the above factors. In the absence of PP cloned T cells the BCDF and MF had only a modest effect on IgA production, whereas in the presence of PP, but not spleen cloned T cells, IgA production was increased. Next, to investigate the effect of T cells derived from a gut-associated lymphoid tissue (GALT), mesenteric lymph nodes (MLN), as well as from spleen on terminal differentiation of postswitch sIgA PP B cells, LPS-driven PP B cells were precultured with the cloned T cells to induce a switch to sIgA, and subsequently cultured with MLN or spleen T cells or a Lyt-2+-depleted T cell subset in the presence of a T-dependent polyclonal mitogen, staphylococcal protein A. Alternatively, in the second culture period BCDF alone was added, instead of T cells and protein A. Here it was found that B cells pre-exposed to switch T cells from PP, but not spleen, were induced to produce greatly increased amounts of IgA in the presence of protein A and T cells or a Lyt-2+-depleted T cell subset as well as in the presence of BCDF alone. Furthermore, in the presence of BCDF alone many B cells expressed cytoplasmic IgA. These observations strongly support the view that the terminal differentiation of postswitch sIgA B cells is governed by helper T cells and macrophages, or factors derived from such cells. Such cells or factors do not affect preswitch B cells.

scholarly journals B Cell–Activating Factor Promotes B Cell Survival in Ectopic Lymphoid Tissues in Nasal Polyps

2021 ◽  
Vol 11 ◽  
Author(s):  
Zhe-Zheng Wang ◽  
Jia Song ◽  
Hai Wang ◽  
Jing-Xian Li ◽  
Qiao Xiao ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Cell Survival ◽  
Stromal Cells ◽  
Caspase 3 ◽  
Lymphoid Tissues ◽  
B Cell Activating Factor ◽  
B Cell Survival ◽  
Active Caspase

Ectopic lymphoid tissues (eLTs) characterized by B cell aggregation contribute to the local immunoglobulin production in nasal polyps (NPs). B cell-activating factor (BAFF) is vital for B cell survival, proliferation, and maturation. The purpose of this study is to investigate whether BAFF is involved in the B cell survival and eLT formation in NPs. The mRNA and protein levels of BAFF in NP tissues with and without eLTs were detected by PCR and ELISA assay, respectively. The cellular sources of BAFF and active caspase-3-positive B cells in NPs were studied by immunofluorescence staining. B cells purified from NP tissues were stimulated with BAFF and were analyzed by flow cytometry. Stromal cells purified from NP tissues were stimulated with lymphotoxin (LT) α1β2, and BAFF levels in culture supernatants were analyzed by ELISA. Compared with those in control tissues and NPs without eLTs, the BAFF levels were elevated in NPs with eLTs. Abundant BAFF-positive cells and few active caspase-3-positive apoptotic B cells were found in NPs with eLTs, in contrast to those in NPs without eLTs. There was a negative correlation between the numbers of BAFF-positive cells and frequencies of apoptotic B cells in total B cells in NP tissues. BAFF protected nasal polyp B cells from apoptosis in vitro. Stromal cells were an important cellular source of BAFF in NPs with eLTs. LTα1β2 induced BAFF production from nasal stromal cells in vitro. We propose that BAFF contribute to eLT formation in NPs by promoting B cell survival.

scholarly journals Immunolocalization of the ICE/Ced-3–Family Protease, CPP32 (Caspase-3), in Non-Hodgkin's Lymphomas, Chronic Lymphocytic Leukemias, and Reactive Lymph Nodes

Blood ◽  
1997 ◽  
Vol 89 (10) ◽  
pp. 3817-3825 ◽  
Author(s):  
Stanislaw Krajewski ◽  
Randy D. Gascoyne ◽  
Juan M. Zapata ◽  
Maryla Krajewska ◽  
Shinichi Kitada ◽  
...  
Keyword(s):  
B Cells ◽  
Lymph Nodes ◽  
B Cell ◽  
Germinal Center ◽  
Caspase 3 ◽  
Large Cell ◽  
B Cell Lymphomas ◽  
Mantle Zone ◽  
Dynamic Regulation ◽  
Hodgkin's Lymphomas

Immunohistochemical analysis of the apoptosis-effector protease CPP32 (Caspase-3) in normal lymph nodes, tonsils, and nodes affected with reactive hyperplasia (n = 22) showed strong immunoreactivity in the apoptosis-prone germinal center B-lymphocytes of secondary follicles, but little or no reactivity in the surrounding long-lived mantle zone lymphocytes. Immunoblot analysis of fluorescence-activated cell sorted germinal center and mantle zone B cells supported the immunohistochemical results. In 22 of 27 (81%) follicular small cleaved cell non-Hodgkin's B-cell lymphomas, the CPP32-immunopositive germinal center lymphocytes were replaced by CPP32-negative tumor cells. In contrast, the large cell component of follicular mixed cells (FMs) and follicular large cell lymphomas (FLCLs) was strongly CPP32 immunopositive in 12 of 17 (71%) and in 8 of 14 (57%) cases, respectively, whereas the residual small-cleaved cells were poorly stained for CPP32 in all FLCLs and in 12 of 17 (71%) FMs, suggesting that an upregulation of CPP32 immunoreactivity occurred during progression. Similarly, cytosolic immunostaining for CPP32 was present in 10 of 12 (83%) diffuse large cell lymphomas (DLCLs) and 2 of 3 diffuse mixed B-cell lymphomas (DMs). Immunopositivity for CPP32 was also found in the majority of other types of non-Hodgkin's lymphomas studied. Plasmacytomas were CPP32 immunonegative in 4 of 12 (33%) cases, in contrast to normal plasma cells, which uniformly contained intense CPP32 immunoreactivity, implying downregulation of CPP32 in a subset of these malignancies. All 12 peripheral blood B-cell chronic lymphocyte leukemia specimens examined were CPP32 immunopositive, whereas 3 of 3 small lymphocytic lymphomas were CPP32 negative, suggesting that CPP32 expression may vary depending on the tissue compartment in which these neoplastic B cells reside. The results show dynamic regulation of CPP32 expression in normal and malignant lymphocytes.

Core 2 branching β1,6-N-acetylglucosaminyltransferase and high endothelial cell N-acetylglucosamine-6-sulfotransferase exert differential control over B- and T-lymphocyte homing to peripheral lymph nodes

Blood ◽  
2004 ◽  
Vol 104 (13) ◽  
pp. 4104-4112 ◽  
Author(s):  
Jean-Marc Gauguet ◽  
Steven D. Rosen ◽  
Jamey D. Marth ◽  
Ulrich H. von Andrian
Keyword(s):  
T Cells ◽  
Endothelial Cell ◽  
T Cell ◽  
B Cells ◽  
Lymph Nodes ◽  
B Cell ◽  
Lymphocyte Homing ◽  
High Endothelial Venules ◽  
Rolling Velocity ◽  
Peripheral Lymph

Abstract Blood-borne lymphocyte trafficking to peripheral lymph nodes (PLNs) depends on the successful initiation of rolling interactions mediated by L-selectin binding to sialomucin ligands in high endothelial venules (HEVs). Biochemical analysis of purified L-selectin ligands has identified posttranslational modifications mediated by Core2GlcNAcT-I and high endothelial cell GlcNAc-6-sulfotransferase (HECGlcNAc6ST). Consequently, lymphocyte migration to PLNs of C2GlcNAcT-I-/- and HEC-GlcNAc6ST-/- mice was reduced; however, B-cell homing was more severely compromised than T-cell migration. Accordingly, intravital microscopy (IVM) of PLN HEVs revealed a defect in B-cell tethering and increased rolling velocity (Vroll) in C2GlcNAcT-I-/- mice that was more pronounced than it was for T cells. By contrast, B- and T-cell tethering was normal in HEC-GlcNAc6ST-/- HEVs, but Vroll was accelerated, especially for B cells. The increased sensitivity of B cells to glycan deficiencies was caused by lower expression levels of L-selectin; L-selectin+/- T cells expressing L-selectin levels equivalent to those of B cells exhibited intravascular behavior similar to that of B cells. These results demonstrate distinct functions for C2GlcNAcT-I and HEC-GlcNAc6ST in the differential elaboration of HEV glycoproteins that set a threshold for the amount of L-selectin needed for lymphocyte homing. (Blood. 2004;104:4104-4112)

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