PubMed Health⌕ Search

Biomedical subjects

M O Dailey

Publications and source records attributed to M O Dailey.

At least 19 recordsLinked to original sources
PubMed2001

Regulation of membrane metalloproteolytic cleavage of L-selectin (CD62l) by the epidermal growth factor domain.

The adhesion molecule L-selectin is cleaved rapidly from the surface of activated leukocytes by tumor necrosis factor-alpha converting enzyme, a cell surface metalloprotease, and also undergoes slower constitutive shedding in unactivated cells. The structural features that render it susceptible to shedding are poorly understood. We therefore analyzed the shedding of a series of mutant and chimeric L-selectin molecules. Although murine L-selectin is cleaved at a specific location in the juxtamembrane region 11 amino acids distal to the cell membrane, this cleavage has little sequence specificity. However, proline substitution at the P2' or P3' position or deletion of the epidermal growth factor (EGF) domain completely blocks the rapid phorbol ester-induced cleavage, but does not affect the slower basal proteolytic shedding. Insertion of the 15-residue membrane-proximal region (MPR) of L-selectin into the heterologous protein B7.2 results in a molecule that undergoes constitutive proteolytic turnover. In contrast, insertion of both the EGF domain and the MPR confers susceptibility to both slow constitutive shedding and the rapid proteolytic cleavage induced by phorbol 12-myristate 13-acetate. These results demonstrate that constitutive and induced L-selectin cleavage are separable processes and that the rapid phorbol ester-induced shedding requires the presence of the EGF domain, a sequence that is remote from the cleavage site.

ADAM Proteins↗
PubMed2001

Characterization of the rapid proteolytic shedding of murine L-selectin.

The structural requirements for L-selectin shedding were studied in murine leukocytes. Upon activation, L-selectin on both lymphocytes and neutrophils undergoes cleavage by a membrane metalloprotease, resulting in the generation of a soluble ectodomain and a membrane-retained 6 kD fragment. Radiochemical sequencing demonstrated a cleavage site in the membrane-proximal region (MPR) between R321 and S322, which is homologous to the human site. Although intact neutrophil L-selectin is larger, it is cleaved at the same, or very close, site. Analysis of several transfectants expressing L-selectin point mutations and chimeric constructs suggest that, like human shedding, the proteolytic process has relatively loose sequence specificity for the substrate site. In addition, some constructs are susceptible to slow constitutive cleavage, but their shedding does not increase upon PMA stimulation, showing that basal and activated shedding are separable processes. Insertion of the 15 amino acid MPR into murine B7.2 conferred upon this molecule susceptibility to constitutive shedding. PMA stimulation results in little or no acceleration of down regulation of this molecule. These results suggest that recognition of both the membrane-proximal cleavage site and of a site distant from the MPR are required for maximal induction of L-selectin shedding.

Animals↗
PubMed2000

Traffic of L-selectin-negative T cells to sites of inflammation.

T cells responding to antigen in vivo down-regulate L-selectin, the lymph node homing receptor, as they develop into activated effector cells. The concomitant up-regulation of the proinflammatory adhesion molecules LFA-1, CD44, and VLA-4 suggests that, after their release into the circulation, they traffic to sites of antigen deposition and inflammation. Previous evidence, however, has suggested a role for L-selectin in the recruitment of both neutrophils and lymphocytes into sites of inflammation, which would indicate that these L-selectin(-) effector cells could not be the precursors of inflammatory cells. We therefore directly tested whether L-selectin(-) T cells activated in vivo are capable of homing to model inflammatory sites. L-selectin(-) cells isolated from mice primed with alloantigen or with a contact sensitizer migrated to inflammation markedly better than L-selectin(+) cells from the same animals. Furthermore, the analogous population of CD44(hi)integrin(hi) cells from intravenously primed L-selectin knockout mice traffic efficiently to inflammatory sites and reject allogeneic skin grafts with normal kinetics. These data demonstrate that the previously described L-selectin(-) population of T cells that differentiate into effectors in spleen and lymph nodes subsequently traffic to inflammatory sites, due in part to their increased expression of other proinflammatory adhesion molecules.

Animals↗
PubMed1999

Selection of CTL escape mutants in mice infected with a neurotropic coronavirus: quantitative estimate of TCR diversity in the infected central nervous system.

Variant viruses mutated in the immunodominant cytotoxic T cell epitope surface (S) glycoprotein S-510-518 are selected in mice chronically infected with mouse hepatitis virus, strain JHM. We determined whether this selection occurred in the presence of an oligoclonal or polyclonal T cell response using soluble MHC/peptide tetramers in direct ex vivo analyses of CNS-derived lymphocytes. A total of 42% (range, 29-60%) of CD8 T cells in the CNS of mice with acute encephalitis recognized epitope S-510-518. A total of 34% (range, 18-62%) of cells from mice with hind limb paralysis (and chronic demyelination) were also epitope specific, even though only virus expressing mutated epitope is detected in these animals. Sequence analysis of the beta-chain CDR3 of 487 tetramer S-510-518-positive cDNA clones from nine mice showed that a majority of clonotypes were identified in more than one mouse. From these analyses, we estimated that 300-500 different CD8 T cell clonotypes responsive to epitope S-510-518 were present in each acutely infected brain, while 100-900 were present in the CNS of each mouse with chronic disease. In conclusion, a polyclonal CD8 T cell response to an epitope does not preclude the selection of T cell escape mutants, and epitope-specific T cells are still present at high levels even after RNA-encoding wild-type sequence is no longer detectable.

Acute Disease↗
PubMed1998

Homing of transgenic gammadelta T cells into murine vaginal epithelium.

The vaginal epithelium of normal mice contains lymphocytes of fetal thymic origin that express an invariant Vgamma4/Vdelta1 TCR. The apparent lack of other gammadelta TCR species suggests that a selection mechanism might operate to regulate the localization of gammadelta T cells at this anatomical site. Selection might be connected to the Vgamma4/Vdelta1 TCR or to some homing characteristic of the fetal thymic lineage that appears at day 17-18 of embryonic life. In the present studies, we investigated whether transgenic gammadelta cells expressing a TCR species characteristic of the subpopulation of gammadelta T cells found in the blood, spleen and lymph would translocate to the vaginal epithelium. We found that the transgenic Vgamma2 TCR+ cells did accumulate in the vagina of transgenic mice. Furthermore, like normal vaginal gammadelta T cells, the transgenic vaginal gammadelta T cells expressed the phenotype of recently activated memory/effector T cells (CD44(hi), CD62L-, CD45RB(lo), CD69+). Vaginal gammadelta T cells in normal mice do not express the CD2 and CD28 antigens, but both of these markers are present on transgenic vaginal gammadelta T cells. We observed that a small fraction of splenic transgenic gammadelta T cells had the same surface phenotype as the vaginal transgenic gammadelta T cells, raising the possibility that the gammadelta T cells present in the vaginal epithelium of transgenic mice originated from the peripheral lymphoid organs. Data in support of this possibility came from experiments in which co-incubation of splenic transgenic gammadelta T cells with vaginal epithelial cell suspensions induced the vaginal gammadelta phenotype on the splenic gammadelta T cells. The finding of transgenic gammadelta T cells in the vaginal epithelium suggests that homing of gammadelta T cells to this site is not restricted to gammadelta T cells that express the V4/NS1 invariant TCR. Furthermore, these findings imply that retention of gammadelta T cells in the vaginal epithelium of normal mice is affected by a Vgamma4/Vdelta1-specific mechanism. The finding of a significant level of apoptosis in the transgenic vaginal gammadelta T cells, but not in the normal vaginal gammadelta T cells, could reflect that the mechanism of retention of Vgamma4/Vdelta1 + in the vaginal epithelium involves selective survival at the site.

Animals↗
PubMed1998

Expression of T lymphocyte adhesion molecules: regulation during antigen-induced T cell activation and differentiation.

The pattern of lymphocyte traffic and migration in vivo is a composite of constitutive recirculation and transient changes induced by interaction with antigen. Naive T lymphocytes in their basal, unstimulated state continuously recirculate throughout the entire host, poised to react to specific antigens that they are programmed to recognize. After interaction with antigen, T cell traffic changes, first with the trapping of reactive cells in antigen-containing lymphoid tissue. Subsequently, the effector cells responding to antigen, accompanied by nonspecific T cells and monocytes, traffic in large numbers to sites of antigen localization, resulting in the localized inflammatory response. Then, as the immune response wanes, memory T cells develop, many of which exhibit still different routes of recirculation. The traffic and tissue localization of leukocytes is regulated by a series of cell surface adhesion molecules that recognize specific ligands on endothelial cells and in the extracellular matrix. Modulation of the expression of these adhesion molecules results in the changes in T cell traffic that are characteristic of each stage of T cell differentiation. Thus, during T cell activation and differentiation, the down-regulation of adhesion receptors specific for lymphoid tissue endothelium and up-regulation of integrins facilitate the targeting of effector cells to sites of inflammation. Subsequent changes in adhesion receptors regulate the traffic of the antigen-specific memory cells. T cell adhesion molecule expression is therefore regulated as a function of the stage of activation and differentiation and, in addition, is influenced by cytokines and the local lymphoid microenvironment.

Animals↗
PubMed1997

Mechanisms of L-selectin regulation by activated T cells.

The activation of T cells through the TCR results in the differential regulation of a set of adhesion molecules that dramatically alters lymphocyte migration and tissue localization properties in vivo. L-selectin, the lymph node homing receptor, is central to the control of lymphocyte recirculation. We examined the regulation of L-selectin as a function of time after activation in vitro. Within an hour of stimulation, T cells down regulate L-selectin, with a 90% loss by 4 h, due to accelerated proteolytic cleavage. Over the course of the following 48 h, surface receptor expression increases markedly. This is due to an increase in L-selectin mRNA, which, in turn, results from increased message stability. During the next several days after activation, L-selectin levels decrease, resulting in L-selectin-negative T cells by 5 to 7 days after stimulation. This decrease occurs faster in CD8 than in CD4 T cells. During this phase of regulation, L-selectin message remains stable even as the level of specific mRNA continuously decreases. This indicates that the L-selectin-negative phenotype of T cells late after activation is due to the down-regulation of gene transcription. These results demonstrate that after stimulation through the TCR, the expression of L-selectin changes in a triphasic pattern, with an initial marked decrease, followed by a transient phase of superinduction and then a loss of expression. These changes are regulated through the complex interactions between several mechanisms at the transcriptional, post-transcriptional, and protein turnover levels.

Animals↗
PubMed1996

Cytokine secretion and adhesion molecule expression by granuloma T lymphocytes in Mycobacterium avium infection.

Mice experimentally infected with Mycobacterium avium develop a chronic disease characterized by widespread noncaseating granulomas. In this report, we describe the phenotype and cytokine secretion profile of these granuloma-infiltrating effector T lymphocytes. In response to specific antigen, granuloma T cells and, to a lesser extent, spleen cells secrete interferon-gamma, but no interleukin-4 or -5. The importance of this Th1-like response to the host was demonstrated by the massively increased bacterial load and lethal disease in interferon-gamma knockout mice. One function of localized cytokine secretion is to recruit inflammatory T cells bearing surface adhesion molecules complementary to counter-receptors on vascular endothelial cells. Granuloma T cells express high levels of these pro-inflammatory adhesion molecules but have down-regulated their expression of L-selectin (CD62L). The expression of these adhesion molecules on granuloma-infiltrating T lymphocytes would alter the migration pathway of these cells and is likely to be important in facilitating the traffic of effector T cells to the granulomatous inflammatory site. In addition, T cells from Schistosoma mansoni granulomas express the same set of adhesion molecules, showing that this phenotype is not specifically dependent upon the Th1 pattern of cytokine secretion.

Animals↗
PubMed1994

Regulation of adhesion molecule expression by CD8 T cells in vivo. II. Expression of L-selectin (CD62L) by memory cytolytic T cells responding to minor histocompatibility antigens.

Activation of murine T cells by Ag or mitogens results in changes in the expression of several cell-surface adhesion molecules that alter the way in which these cells migrate and localize in tissues in vivo. As naive CD8 precursor cells in lymph nodes (LN) differentiate into effector CTL in response to a skin allograft, they up-regulate their expression of Pgp-1 (CD44), VLA-4, and LFA-1 (CD11a/18), while down-regulating L-selectin (CD62L). All cytolytic activity is therefore present in this minor population of L-selectin- Pgp-1high LN T cells. We now report that, late after rejection of minor histocompatibility Ag-disparate skin grafts, the majority of memory CD8 T cells express both L-selectin and Pgp-1 and thus would be expected to migrate via the classical route of recirculation through LN. Furthermore, restimulation of these memory cells by Ag causes them to down-regulate L-selectin, so that memory-effector cells have the same L-selectin- Pgp-1high phenotype as do primary effector cells. These results are in contrast to recent reports that murine and ovine CD4 memory cells do not express L-selectin or recirculate through LN high endothelial venules. In addition, although virgin and naive CD4 cells may be divided based upon their expression of CD45RA or CD45RB, memory CD8 cells cannot be differentiated by their expression of CD45 isoforms.

Animals↗
PubMed1994

Expression and regulation of adhesion molecules by gamma delta T cells from lymphoid tissues and intestinal epithelium.

T cells bearing the gamma delta T cell receptor localize largely in epithelial tissues, but are also present at low frequency in organized secondary lymphoid organs. To assess the role of cell surface adhesion molecules in the traffic and tissue localization of gamma delta T cells, we compared the expression of these molecules on both alpha beta and gamma delta T cells in several lymphoid and non-lymphoid organs. In the gut epithelium, gamma delta cells express less LFA-1 (CD11a), Pgp-1 (CD44), and alpha 4 integrin than the corresponding alpha beta cells. In lymph nodes (LN) and Peyer's patches (PP), adhesion molecule expression by gamma delta cells is heterogeneous, with some of the cells having a phenotype similar to that of intraepithelial gamma delta cells and the rest expressing high levels of CD44 and L-selectin (CD62L) but lower beta 7 and alpha M290, a phenotype more like lymph node alpha beta cells. Therefore, the particular set of adhesion molecules expressed by a T cell is dependent, in part, on its anatomic location. Superimposed upon this, however, are differences in expression that are based on the type of T cell; LN and PP gamma delta T cells express less CD44 but much more beta 7, alpha M290 and ICAM-1 (CD54) than alpha beta T cells in the same organ. The differences in adhesion molecules between alpha beta and gamma delta cells are not due simply to differences in their activation status, because these molecules are regulated differently after activation through the T cell receptor (TcR)/CD3 complex. The differential expression of adhesion molecules on cells bearing a particular TcR V region suggests that distinct adhesion phenotypes may arise from prior contact with specific antigen and resultant cell activation in vivo. Lastly, the presence of high level expression of alpha 4 beta 7 and alpha M290 on L-selectinlo gamma delta cells in lymph nodes suggests that these gamma delta cells may be uniquely capable of migrating to the gut. The differences in adhesion molecule expression and regulation between gamma delta and alpha beta T cells could explain, in part, the distinct homing and tissue localization of these T cell subsets in vivo.

Animals↗
PubMed1992

Regulation of adhesion molecule expression by CD8 T cells in vivo. I. Differential regulation of gp90MEL-14 (LECAM-1), Pgp-1, LFA-1, and VLA-4 alpha during the differentiation of cytotoxic T lymphocytes induced by allografts.

A variety of adhesion molecules regulate the traffic and tissue localization of lymphocytes in vivo by mediating their binding to vascular endothelial cells. The homing receptor gp90MEL-14 (gp90), also known as LECAM-1 or L-selectin, mediates the adhesion of lymphocytes to specialized high endothelial venules in lymph nodes (LN) and is the primary molecule regulating lymphocyte recirculation and homing to LN, whereas other adhesion molecules have a major role in the localization of lymphocytes in inflammatory sites. We used four-color flow cytometric analysis to examine the regulation of adhesion receptor expression on LN CD8 T cells responding to skin allografts in vivo. In normal mice, greater than 95% of LN CD8 T cells are gp90+, being either gp90+Pgp1- (Population (Pop.) 1 or gp90+Pgp-1+ (Pop.2). Allografting induces the down-regulation of gp90 and up-regulation of Pgp-1 on a subset of cells, resulting in the appearance of CD8+gp90-Pgp-1hi (Pop. 3) cells. Pop. 3 cells also express high levels of LFA-1, ICAM-1, and ICAM-2, and a subset of them are VLA-4 alpha-positive. Purified Pop. 3 cells have potent cytolytic activity directed against donor alloantigen, whereas no such activity is present in Pop. 1 or 2 cells. Correlating with this is the high granzyme activity in Pop. 3 cells. In addition, Pop. 3 lymphocytes, but not Pop. 1 or 2, secrete a large amount of IFN-gamma in response to Ag. Finally, the CD8 T cells that infiltrate sponge matrix allografts are markedly enriched for the Pop. 3 subset. These results show that, during the immune response to alloantigen in vivo, a small subset of CD8 T cells down-regulates the LN homing receptor while increasing the expression of other adhesion molecules, as they differentiate into highly active cytolytic T lymphocytes. Thus, the differential regulation of LN homing receptors and receptors for peripheral vascular endothelium provides a mechanism that would redirect the traffic of activated effector cells away from lymphoid tissue and to sites of Ag deposition, where they would participate in the inflammatory response.

Animals↗
PubMed1992

Immune response to a murine coronavirus: identification of a homing receptor-negative CD4+ T cell subset that responds to viral glycoproteins.

The lymphocyte proliferative response to mouse hepatitis virus, strain JHM (MHV-JHM), a well-described cause of chronic and acute neurological infections, has been studied using vaccinia virus recombinants expressing individual MHV proteins. The surface (S) and transmembrane (M) glycoproteins were the most active proteins in causing proliferation of lymphocytes isolated from immunized adult mice, whereas lymphocytes from persistently infected mice proliferated only in response to the S protein. The cells from immunized mice which proliferated most actively in response to MHV were positive for the CD4 antigen and secreted interferon-gamma. In addition, the most responsive subset of cells did not express gp90MEL-14, the lymph node-specific homing receptor. The results identify a subpopulation of CD4+ T cells that may be an important component of the cell-mediated immune response to this virus. The data also suggest that response to the M protein is important in preventing disease progression in C57BL/6 mice since cells which recognize this protein are absent from persistently infected mice.

Animals↗
PubMed1990

Expression of the CD11/CD18, leukocyte adhesion molecule 1, and CD44 adhesion molecules during normal myeloid and erythroid differentiation in humans.

We have used three-color flow cytometry to investigate the pattern of expression of the CD11/CD18, CD44, and leukocyte adhesion molecule 1 (LAM-1) adhesion molecules during myeloid and erythroid differentiation in humans. The earliest myeloid cells, identified as CD33loCD15-, were exclusively CD44hi but contained both leukocyte function-associated antigen 1 (LFA-1hi) and LFA-1lo cells, as well as LAM-1+ and LAM-1- cells. This CD33loCD15- myeloid subpopulation expressed only low levels of CD11c and failed to express CD11b, CD14, or any lymphoid (CD3, CD16, CD19) antigens or glycophorin. Commitment to monocyte differentiation, suggested by the presence of an LFA-1hi CD11c+ subset within the CD33loCD15- subpopulation, was clearly signaled by upregulation of CD33; these monocyte-lineage committed cells were exclusively CD33hi, CD44hi, CD11ahi, CD11c+, and exhibited a broad range of intensity of CD15 expression. Later stages of monopoiesis were identified by acquisition of CD11b, and subsequently of CD14. Myeloid cells committed to granulopoiesis remained LFA-1lo, and underwent a sharp upregulation of CD15 along with downregulation of both CD33 and CD44. Successive stages of granulocyte development were marked by expression of CD11b and, subsequently, of CD16. The earliest cells capable of erythroid differentiation were CD44hi, LFA-1lo, and LAM-1+. Both LFA-1 and LAM-1 were lost before the onset of glycophorin (glyco) expression, whereas CD44 expression remained high on glyco+ cells, which also expressed CD45. CD44 expression was intermediate on glyco+ CD71+ cells, and low on glyco+ CD45- CD71- cells, similar to normal, circulating erythrocytes. Our results allow us to phenotypically define discrete stages in the normal development of monocytes, neutrophils, and erythrocytes. The expression of LFA-1, LAM-1, and high levels of CD44 on the most primitive hematopoietic cells detectable by flow cytometry suggests that at least some of these molecules are critically involved in leukocyte adhesion during development.

Antigens, Differentiation↗
PubMed1990

Rapid modulation of homing receptors (gp90MEL-14) induced by activators of protein kinase C. Receptor shedding due to accelerated proteolytic cleavage at the cell surface.

Lymphocyte entry into lymph nodes and Peyer's patches is initiated by the adhesion of the lymphocytes to specialized postcapillary high endothelial venules (HEV). The binding of lymphocytes to lymph node HEV is mediated by the cell surface receptor gp90MEL-14 (gp90). Previous work has shown that gp90 is down-regulated over a period of days after mitogenic or mixed lymphocyte reaction stimulation of T lymphocytes. In our study, it is shown that stimulation of lymphocytes with activators of protein kinase C (PKC), such as PMA or 1-oleoyl 2-acetyl-glycerol, results in the nearly complete loss of surface expression of gp90 within 1 h. Pretreatment of the cells with H-7 or staurosporine, PKC inhibitors, but not HA1004, a general protein kinase inhibitor, prevents the loss of gp90MEL-14. Within 15 min of stimulation of PKC, a novel form of gp90 can be immunoprecipitated from the supernatant of stimulated cells. Upon deglycosylation, this soluble gp90 polypeptide is shown to be 12 kDa smaller than the cell surface protein. Peptide mapping showed identical patterns for surface and soluble receptor, confirming that the soluble Ag is related to the cell membrane protein. Together, these experiments suggest that activation of PKC results in the proteolytic cleavage of gp90MEL-14, resulting in receptor shedding and the inability of the lymphocytes to adhere to HEV endothelium. Furthermore, because supernatant from unstimulated, normal lymphocytes also contains a small amount of the low Mr form of gp90, cell surface proteolysis may be part of the normal turnover of this receptor glycoprotein. These experiments suggest that PKC may play a role in the regulation of lymphocyte traffic to lymphoid tissues.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1989

A novel and inexpensive source of allophycocyanin for multicolor flow cytometry.

Allophycocyanin (APC) belongs to a family of phycobiliproteins that are well suited as fluorescent reagents for flow cytometric analysis, since they have a broad excitation spectrum, a large Stoke's shift and they fluoresce with a high quantum yield. The widespread use of APC has been limited by the availability of raw material and high cost of the purified phycobiliprotein. We have assessed the suitability of dry, powdered Spirulina platensis, available at health food stores, as an inexpensive source of APC. APC was extracted from Spirulina platensis by overnight treatment with lysozyme, followed by ammonium sulfate precipitation. APC was then separated from phycocyanin (the only other major phycobiliprotein in Spirulina) by elution of bound material from an hydroxylapatite column using an increasing continuous phosphate gradient. APC isolated in this manner retained its normal trimeric structure. The absorbance and fluorescence excitation and emission spectra of the purified phycobiliproteins were identical to those previously shown for C-PC and APC. APC can be stored concentrated at 4 degrees C, frozen at -70 degrees C, or as a saturated ammonium sulfate precipitate, with no subunit dissociation or change in spectral properties. Moreover, APC has been conjugated to monoclonal and polyclonal antibodies for use in multicolor FACS analysis, with the conjugated antibody activity remaining stable for at least 2 years. Thus, this procedure is a simple, cost-effective method for preparing reagents for multicolor immunofluorescence and flow cytometry.

Cyanobacteria↗
PubMed1989

A family of cell-surface glycoproteins defined by a putative anti-endothelial cell receptor antibody in man.

An efficient immune response depends directly on the ability of lymphocytes and other blood borne leukocytes to leave the blood and enter lymphoid organs and other sites of immune response or inflammation. A new murine mAb termed 515 recognizes a 85- to 90-kDa structure involved in lymphocyte binding to specialized endothelium in postcapillary venules of lymphoid organs (high endothelial venules). In crossed immunoprecipitations followed by SDS-PAGE analysis, 515 appears to be identical to the antilymphocyte homing receptor mAb, Hermes-1. We show here that 515 recognizes peripheral blood leukocytes of all classes examined, but, like Hermes-1, fails to recognize germinal center cells or nearly all cortical (but not medullary) thymocytes. In addition, we demonstrate that 515 recognizes both fibroblasts and epidermal keratinocytes, both in situ and in cultured cell lines. Immunoprecipitation and SDS-PAGE analysis reveals that 515-defined Ag from T lymphocytes, neutrophils, and the epidermal keratinocyte cell line HaCaT are clearly distinct, both before and after treatment with peptide N-glycosidase F, which removes all asparagine-linked oligosaccharides. In contrast, the Mr of 515-defined Ag from T cells and fibroblasts appear indistinguishable. Thus, the 515 mAb recognizes a broadly distributed family of glycoproteins which may be involved in a variety of adhesive functions.

Animals↗
PubMed1989

Expression of adhesion structures during B cell development in man.

We have used three-color flow cytometry to study the expression of adhesion structures during B cell development in man. The results indicate that the cell-surface molecule(s) recognized by 515, a mAb which defines a broadly expressed family of cell-surface glycoproteins that includes lymphocyte homing receptors, exhibit a clear bimodal distribution (515lo and 515hi); 515hi cells were found exclusively on more mature B cells which already expressed high levels of CD20. Earlier, less mature B cells, identified by their expression of CD10, were uniformly 515lo. In contrast, the CD11a/LFA-1 Ag was acquired gradually over the course of B cell development. B cells which expressed high levels of CD20 expressed three to six times as much CD11a/LFA-1 as cells which expressed CD10. Interestingly, expression of the 515hi phenotype was tightly correlated with that of Leu-8, a marker previously shown to define maturational and functions subsets of B cells. These data document the coordinated regulation of multiple cell surface structures during B cell ontogeny, and demonstrate that adhesion structures necessary for proper B cell function are precisely up-regulated during B cell differentiation in man.

Adult↗