scholarly journals K21-Antigen: A Molecule Shared by the Microenvironments of the Human Thymus and Germinal Centers

1998 ◽  
Vol 6 (1-2) ◽  
pp. 41-52 ◽  
Author(s):  
Nesrina Imami ◽  
Heather M. Ladyman ◽  
Bjarne Vincents ◽  
Abdulhamid Al-Tubuly ◽  
Jona Freysdóttir ◽  
...  
Keyword(s):  
T Cells ◽  
B Cells ◽  
B Cell ◽  
Intracellular Localization ◽  
Flow Cytometric Analysis ◽  
Germinal Centers ◽  
Lymphoid Cells ◽  
Thymic Epithelial Cells ◽  
Lymphoid Tissues ◽  
Human Thymus

The mouse IgG1 monoclonal antibody (mAb) K21 recognizes a 230-kD molecule (K21-Ag) on Hassall's corpuscles in the human thymus. This mAb also stains cultured thymic epithelial cells as well as other epithelial cell lines, revealing a predominant intracellular localization. Further analysis with mAb K21 on other lymphoid tissues showed that it also stains cells within the germinal centers of human tonsils, both lymphoid (B) cells and some with the appearance of follicular dendritic cells. Double immunostaining of tonsil sections shows that K21-Ag is not expressed by T cells, whereas staining with anti-CD22 and -CD23 mAb revealed some doublepositive cells. A subpopulation of the lymphoid cells express the K21-Ag much more strongly. This K21++/CD23++subpopulation of cells is localized in the apical light zone of germinal centers, suggesting that K21-Ag may be an important marker for the selected centrocytes within germinal centers and may play a role in B-cell selection and/or development of B-cell memory. Flow cytometric analysis showed that K21-Ag is expressed on the surface of a very low percentage of thymocytes, tonsillar lymphocytes, and peripheral blood mononuclear cells. Analysis of purified/separated tonsillar T and B lymphocytes showed that T cells do not express the K21-Ag; in contrast, B cells express low levels of the K21-Ag, and this together with CD23 is upregulated after mitogenic stimulation. Our data therefore raise the possibility that the K2l- Ag may play a role in B-lymphocyte activation/selection.

scholarly journals Identification of a B cell differentiation factor(s) spontaneously produced by proliferating T cells in murine lupus strains of the lpr/lpr genotype.

1983 ◽  
Vol 157 (2) ◽  
pp. 730-742 ◽  
Author(s):  
G J Prud'Homme ◽  
C L Park ◽  
T M Fieser ◽  
R Kofler ◽  
F J Dixon ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Differentiation ◽  
B Cells ◽  
B Cell ◽  
Mouse Strain ◽  
Interleukin 2 ◽  
Lymphoid Cells ◽  
B Cell Differentiation ◽  
Differentiation Factor ◽  
Cell Differentiation Factor

Lymph node and spleen cells of the autoimmune MRL/Mp-lpr/lpr mouse strain spontaneously produce (in the absence of mitogenic stimulation) a factor(s) that induces B cell differentiation. This factor is not produced by the congenic MRL/n mouse strain that lacks the lpr gene or by normal mouse strains. However, lymphoid cells of the B6-lpr/lpr (B6/1) strain also produce a B cell differentiation factor. Although the factor acts on resting B cells, its effect is greatly magnified by activating the B cells with anti-mu or lipopolysaccharide. MRL/l mice begin producing the factor as early as 1 mo of age but levels increase with age and appearance of lymphoproliferation. Cell depletion studies reveal that this factor is produced by T cells of the Lyt-1+2-phenotype. Because of its association with the lpr/lpr genotype, we term this B cell differentiation factor L-BCDF. Functional analysis of L-BCDF reveals that it acts regardless of cell density in culture and in the absence of interleukin 2 (IL-2). In fact, the increase in the production of L-BCDF by MRL/1 T cells with aging occurs concomitantly with a marked decrease in their ability to produce IL-2. No T cell replacing factor activity or B cell growth factor-like activity can be detected in MRL/l-derived supernatants. L-BCDF induces both IgM and IgG synthesis in lipopolysaccharide-activated B cells; however, it has a greater effect on IgG secretion. In particular, the production of IgG1, IgG2a, and IgG2b are markedly enhanced in the presence of L-BCDF. The spontaneous production of L-BCDF by T cells of SLE mice of lpr/lpr genotype suggests an association of this factor with autoimmunity.

scholarly journals Viral Superantigen Drives Extrafollicular and Follicular B Cell Differentiation Leading to Virus-specific Antibody Production

1997 ◽  
Vol 185 (3) ◽  
pp. 551-562 ◽  
Author(s):  
Sanjiv A. Luther ◽  
Adam Gulbranson-Judge ◽  
Hans Acha-Orbea ◽  
Ian C.M. MacLennan
Keyword(s):  
T Cells ◽  
Cell Differentiation ◽  
B Cells ◽  
B Cell ◽  
Antibody Production ◽  
Specific Antibody ◽  
Germinal Centers ◽  
B Cell Differentiation ◽  
Virus Specific Antibody ◽  
Specific Antibody Production

Mouse mammary tumor virus (MMTV[SW]) encodes a superantigen expressed by infected B cells. It evokes an antibody response specific for viral envelope protein, indicating selective activation of antigen-specific B cells. The response to MMTV(SW) in draining lymph nodes was compared with the response to haptenated chicken gamma globulin (NP-CGG) using flow cytometry and immunohistology. T cell priming occurs in both responses, with T cells proliferating in association with interdigitating dendritic cells in the T zone. T cell proliferation continues in the presence of B cells in the outer T zone, and B blasts then undergo exponential growth and differentiation into plasma cells in the medullary cords. Germinal centers develop in both responses, but those induced by MMTV(SW) appear later and are smaller. Most T cells activated in the T zone and germinal centers in the MMTV(SW) response are superantigen specific and these persist for weeks in lymph nodes draining the site MMTV(SW) injection; this contrasts with the selective loss of superantigen-specific T cells from other secondary lymphoid tissues. The results indicate that this viral superantigen, when expressed by professional antigen-presenting cells, drives extrafollicular and follicular B cell differentiation leading to virus-specific antibody production.

scholarly journals Flow cytometric analysis of the Hermes homing-associated antigen on human lymphocyte subsets

Blood ◽  
1989 ◽  
Vol 74 (2) ◽  
pp. 751-760 ◽  
Author(s):  
J de los Toyos ◽  
S Jalkanen ◽  
EC Butcher
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
Human Lymphocyte ◽  
High Surface ◽  
Interleukin 2 ◽  
Flow Cytometric Analysis ◽  
Surface Glycoprotein ◽  
Lymphoid Tissues ◽  
High Endothelial Venules

Abstract The homing of lymphocytes is controlled by interactions with high endothelial venules (HEV), specialized vessels that define sites of lymphocyte extravasation into lymph nodes and inflamed tissues. In humans, lymphocyte-HEV binding involves a lymphocyte surface glycoprotein (GP) of 85 to 95 kd (CD44, H-CAM), defined by monoclonal antibody (MoAb) Hermes-1. To define the expression of this homing- associated adhesion molecule during human lymphocyte development, we performed two-color immunofluorescence analyses of human bone marrow (BM), thymus, peripheral blood (PB), and tonsillar lymphocytes. The highest levels of Hermes-1 antigen are displayed by circulating B and T cells in the blood, which are uniformly positive and bear roughly twice the level of antigen present on mature lymphocytes within organized lymphoid tissues and BM. “Immature” (CD4+, CD8+) T cells in the thymus are Hermes-1lo to-, whereas thymocytes of mature phenotype (CD4+ or CD8+) are positive. The Hermes-1 antigen is present at high levels on the same population of thymocytes that bears high surface levels of CD3, a component of the T-cell antigen receptor complex, suggesting that levels of T-cell homing and antigen receptors characteristic of mature peripheral T cells appear coordinately during thymocyte maturation/selection. Essentially all T cells in the periphery are Hermes-1hi, including T blasts, and the homing-associated antigen is maintained at high levels on T cells stimulated in vitro by phytohemagglutinin (PHA) and on interleukin-2 (IL-2) maintained T-cell clones and lines. In contrast, although most resting IgD+ B cells are positive a significant fraction of B cells in tonsils are Hermes-1lo to- ; these cells are predominantly PNAhi, IgD-, and CD20hi, a phenotype characteristic of sessile, activated B cells in germinal centers. In all lymphocyte populations examined, there is a linear correlation in staining for Hermes-1 and for Hermes-3, an antibody that defines a distinct functionally important epitope on this molecule. The results demonstrate a precise regulation of this homing-associated antigen during lymphocyte differentiation.

scholarly journals Gap-Junction Communication Pathways in Germinal Center Reactions

1998 ◽  
Vol 6 (1-2) ◽  
pp. 111-118 ◽  
Author(s):  
Tibor Krenacs ◽  
Martin Rosendaal
Keyword(s):  
B Cells ◽  
Gap Junctions ◽  
B Cell ◽  
Germinal Center ◽  
Lucifer Yellow ◽  
Cell Communication ◽  
Germinal Centers ◽  
Lymphoid Tissues ◽  
Human Tonsil ◽  
Cell Fractions

Intercellular channels called gap junctions enable multicellular organisms to exchange information rapidly between cells. Though gap junctions are held to be ubiquitous in solid tissues, we have only recently found them in the lymphoid organs. Functional direct cell-cell communication has now been confirmed by us and other groups in bone marrow, thymus, and in secondary lymphoid tissues. What functions do they serve in the lymphoreticular system where, so far, only cytokines/growth factors and adhesion molecules have been considered as regulators? Here we show evidence for and refer to published work about functional direct cellcell communication through gap junctions in germinal center reactions and make proposals for their role in the immune response.We found a large amount of the connexin43 (Cx43) gap junctions in the germinal centers of secondary lymphoid follicles. Ultrastructurally and immunohistologically, most of the junctions were detected on the processes of follicular dendritic cells (FDC) enveloping nondividing centrocytes in the light zone of germinal centers where B-cell selection is thought to take place. Further support for this finding came by revealing the Cx43 mRNAin situat the same location as the protein. On antigen challenge, gap junctions appeared on the FDC as they formed meshworks in germinal centers. In order to find out which germinal center cells communicate directly, we separated FDC-rich, low-density, B-cell fractions from human tonsil. In culture, we injected single FDC with the low-molecular-weight fluorescent dye, Lucifer Yellow (Mr 457 Da), which passed between adjacent FDC and sometimes from FDC to B cells.Based on these findings and their assigned functions in other tissues, gap junctions may contribute to germinal center reactions in the following ways: (1) they may regulate follicle pattern formation by controlling FDC growth, (2) they may be involved in FDC-B-cell signaling contributing to the final rescue of selected B cells from apoptosis, and (3) they may enable FDC to work as a functional syncytium providing a cellular internet for integrating germinal center events. Data supporting these interpretations are briefly discussed.

scholarly journals Germinal Centers without T Cells

2000 ◽  
Vol 191 (3) ◽  
pp. 485-494 ◽  
Author(s):  
Carola García de Vinuesa ◽  
Matthew C. Cook ◽  
Jennifer Ball ◽  
Marion Drew ◽  
Yvonne Sunners ◽  
...  
Keyword(s):  
T Cells ◽  
B Cells ◽  
B Cell ◽  
Germinal Center ◽  
High Efficiency ◽  
Germinal Centers ◽  
Affinity Maturation ◽  
High Affinity ◽  
Safe Mechanism ◽  
Germinal Center Formation

Germinal centers are critical for affinity maturation of antibody (Ab) responses. This process allows the production of high-efficiency neutralizing Ab that protects against virus infection and bacterial exotoxins. In germinal centers, responding B cells selectively mutate the genes that encode their receptors for antigen. This process can change Ab affinity and specificity. The mutated cells that produce high-affinity Ab are selected to become Ab-forming or memory B cells, whereas cells that have lost affinity or acquired autoreactivity are eliminated. Normally, T cells are critical for germinal center formation and subsequent B cell selection. Both processes involve engagement of CD40 on B cells by T cells. This report describes how high-affinity B cells can be induced to form large germinal centers in response to (4-hydroxy-3-nitrophenyl) acetyl (NP)-Ficoll in the absence of T cells or signaling through CD40 or CD28. This requires extensive cross-linking of the B cell receptors, and a frequency of antigen-specific B cells of at least 1 in 1,000. These germinal centers abort dramatically at the time when mutated high-affinity B cells are normally selected by T cells. Thus, there is a fail-safe mechanism against autoreactivity, even in the event of thymus-independent germinal center formation.

scholarly journals Differential effects of fingolimod on B-cell populations in multiple sclerosis

2014 ◽  
Vol 20 (10) ◽  
pp. 1371-1380 ◽  
Author(s):  
Masakazu Nakamura ◽  
Takako Matsuoka ◽  
Norio Chihara ◽  
Sachiko Miyake ◽  
Wakiro Sato ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
B Cells ◽  
B Cell ◽  
Mononuclear Cells ◽  
Memory B Cells ◽  
Lymphoid Cells ◽  
Oral Drug ◽  
Cell Populations ◽  
Lymphoid Tissues ◽  
Ki 67

Background: Fingolimod is an oral drug approved for multiple sclerosis (MS) with an ability to trap central memory T cells in secondary lymphoid tissues; however, its variable effectiveness in individual patients indicates the need to evaluate its effects on other lymphoid cells. Objective: To clarify the effects of fingolimod on B-cell populations in patients with MS. Methods: We analysed blood samples from 9 fingolimod-treated and 19 control patients with MS by flow cytometry, to determine the frequencies and activation states of naive B cells, memory B cells, and plasmablasts. Results: The frequencies of each B-cell population in peripheral blood mononuclear cells (PBMC) were greatly reduced 2 weeks after starting fingolimod treatment. Detailed analysis revealed a significant reduction in activated memory B cells (CD38int-high), particularly those expressing Ki-67, a marker of cell proliferation. Also, we noted an increased proportion of activated plasmablasts (CD138+) among whole plasmablasts, in the patients treated with fingolimod. Conclusions: The marked reduction of Ki-67+ memory B cells may be directly linked with the effectiveness of fingolimod in treating MS. In contrast, the relative resistance of CD138+ plasmablasts to fingolimod may be of relevance for understanding the differential effectiveness of fingolimod in individual patients.

scholarly journals A Novel P-Selectin Glycoprotein Ligand-1 Monoclonal Antibody Recognizes an Epitope Within the Tyrosine Sulfate Motif of Human PSGL-1 and Blocks Recognition of Both P- and L-Selectin

Blood ◽  
1998 ◽  
Vol 91 (1) ◽  
pp. 154-164 ◽  
Author(s):  
Karen R. Snapp ◽  
Han Ding ◽  
Kristin Atkins ◽  
Roger Warnke ◽  
Francis W. Luscinskas ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
T Cells ◽  
B Cells ◽  
Nk Cells ◽  
Flow Cytometric Analysis ◽  
Lymphoid Cells ◽  
B Cell Differentiation ◽  
Tyrosine Sulfation ◽  
Color Flow ◽  
Cos Cells

Interactions between P-selectin and P-selectin glycoprotein ligand-1 (PSGL-1) mediate the earliest “rolling” of leukocytes on the lumenal surface of endothelial cells at sites of inflammation. Previously, PSGL-1 has been shown to be the primary mediator of interactions between neutrophils and P-selectin, but studies on the ability of PSGL-1 to mediate interactions between P-selectin and other subsets of leukocytes have yielded variable and conflicting results. A novel IgG monoclonal antibody (MoAb) to human PSGL-1 was generated, and the specificity of this MoAb was confirmed by both flow cytometric analysis and Western blotting of cells transfected with human PSGL-1. This newly developed MoAb, KPL1, inhibited interactions between P-selectin expressing COS cells and either HL60 cells, neutrophils, or lymphocytes. Furthermore, KPL1 completely inhibited interactions between P-selectin and either purified CD4 T cells or neutrophils in a flow assay under physiological conditions, but had no effect on interactions of T cells or neutrophils with E-selectin. In addition, KPL1 blocked interactions between lymphoid cells transfected with L-selectin and COS cells expressing PSGL-1. The KPL1 epitope was mapped to a site within a consensus tyrosine sulfation motif of PSGL-1, previously shown to be essential for interaction with P-selectin and now shown to be essential for interaction with L-selectin, and to be distinct from the epitope identified by the PL1 function blocking anti-PSGL-1 MoAb. Two-color flow cytometry of normal leukocytes showed that while natural killer (NK) cells (CD16+), monocytes, CD4 and CD8 T cells, and α/β and γ/δ T cells were uniformly positive for PSGL-1, B cells expressed low levels of the KPL1 epitope. This low level of KPL1 staining was also observed immunohistologically in germinal centers, which had no detectable KPL1 staining, whereas T-cell areas (interfollicular region) were positive for KPL1. Interestingly, plasma cells in situ and interleukin-6–dependent myeloma cell lines were KPL1+. Thus, PSGL-1 is expressed on essentially all blood neutrophils, NK cells, B cells, T cells, and monocytes. Variation in tyrosine sulfation during B-cell differentiation may affect the ability of B cells to interact with P- and L-selectin.

A Profile of 648 Signaling Network Events Identifies Cell Subsets with Diverse, Abnormal Responses to Lymphocyte Stimuli within Follicular Lymphoma Tumors.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 356-356 ◽  
Author(s):  
Jonathan M. Irish ◽  
Faye Y. Hsu ◽  
Jeff P. Sharman ◽  
Roch Houot ◽  
Joshua D. Brody ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
Follicular Lymphoma ◽  
B Cell ◽  
Cell Survival ◽  
Signaling Network ◽  
Lymphoid Cells ◽  
Network Activity ◽  
T Cell Subsets

Abstract Signal transduction plays a key role in cell survival, and changes to signaling are frequently implicated in tumor initiation and progression. We sought to identify abnormal variation in signaling network activity within primary tumor samples obtained prior to treatment from patients with follicular lymphoma (FL). We previously showed that altered B cell receptor (BCR) signaling distinguishes tumor B cells from the non-malignant host B cells in FL tumors. Here we extend this approach and use flow cytometry to measure 648 signaling events in live lymphoid cells from more than 25 lymphoma specimens and healthy controls. We combined 9 previously identified BCR stimulation conditions with inputs from CD40, interleukin 4, interferons (IFNs), and more than 10 other environmental cues that govern the development and activity of lymphocytes. Fluorescent cell barcoding allowed simultaneous staining and analysis of phospho-protein activation under all 27 stimulation conditions within a single tube. The activation of key phospho-protein nodes throughout lymphocyte signaling networks, including Syk, Erk1/2, Btk, Src family kinases, cCbl, p38, NFkB, Akt, Stat1, Stat3, Stat6, and Stat5, was measured under each of the 27 stimulation conditions. Measurements of phospho-protein responses to stimulation were combined with detection of the Bcl-2 oncogene, B and T cell lineage markers in each cell. This panel allowed us to characterize signaling in the heterogeneous cell subsets found within each patient’s tumor sample. Tumor B cells, host tumor infiltrating T cells, non-malignant B cells were all distinguished by contrasting signaling profiles. In some cases, subsets of tumor B cells with differences in signaling network topology were observed within the tumor B cell population. This result suggests that signaling can distinguish between tumor sub-clones and could be used to measure tumor heterogeneity. As previously reported, little variation in signaling was observed among healthy peripheral blood B and T cell samples from different individuals. Abnormally low host T cell signaling was commonly observed within the tumor infiltrating T cells infiltrating FL tumors. Further analysis of tumor T cell subsets indicated that a high proportion of infiltrating T cells expressed CD4 and FoxP3. Taken together, these results support the hypothesis that FL tumor B cells promote suppressed signaling in the T cells of the patient and may modulate the immune response against the tumor. In FL tumor B cells, BCR and IFN signaling frequently triggered Stat5 phosphorylation, but not Stat1 phosphorylation. These results are consistent with the hypothesis that Stat5 initiates genetic programs that support cancer cell survival and proliferation, whereas Stat1 promotes immunogenicity and cooperates with the p53 tumor suppressor protein. In contrast with healthy B cells, loss of the response to CD40L, altered PKC signaling, and variable responses to BCR crosslinking were all seen in FL tumor B cells. The patterns of abnormal signaling we observed in tumor B cells and tumor infiltrating T cells suggest that measuring the activity of key signaling network nodes can identify targets for therapeutic attention in FL.

Diagnostic and Therapeutic Implications of Expression and Phosphorylation of the Translation Regulatory Protein 4E-Binding Protein (BP)-1 in B-Cell Lymphomas and Reactive Lymphoid Tissues.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3919-3919
Author(s):  
Mary J. Ninan ◽  
Ajay Rawal ◽  
Dhatri Kodali ◽  
Hector Mesa ◽  
Manish Patel ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
B Cell ◽  
Marginal Zone ◽  
Germinal Centers ◽  
Lymphoid Tissues ◽  
Follicular Dendritic Cells ◽  
Cellular Specificity ◽  
Follicular Dendritic ◽  
Hodgkin's Lymphomas

Abstract Abstract 3919 Poster Board III-855 Identifying pathogenic mechanisms that contribute to the development of lymphomas and influence clinical behavior is critical for developing targeted therapies, and selecting patients who may benefit from such drugs. An important level of control of gene expression occurs during initiation of cap-mediated mRNA translation by the eukaryotic initiation factor-4F (eIF-4F) trimolecular complex (eIF-4E, eIF-4G and eIF-4A), in which eIF-4E is rate limiting and oncogenic. eIF-4F hyperactivity plays a key role in human cancers by mediating expression of proteins critical for cell growth, transformation and tumorigenesis. eIF-4F activity is controlled by repressor eIF-4 binding proteins (BPs). 4E-BP1 activity is regulated by phosphorylation. Hypo/non-phosphorylated 4E-BP1 is active, binds eIF-4E and impedes eIF-4F formation, blocking translation and inducing apoptosis. Phosphorylation of 4E-BP1 (p4E-BP1) releases bound eIF-4E, which initiates cap-dependent translation. Because only limited information is available on the expression and phosphorylation of 4E-BP1 in lymphomas, and since agents (e.g., antisense oligonucleotides and small molecules) that target eIF-4E have been developed, we examined the frequency and level of expression of 4E-BP1 and its phosphorylation in various subtypes of mature B cell non-Hodgkin's lymphomas (BCL). Forty-six BCLs (12 follicular [FL], 13 diffuse large B-cell [DLBCL], 7 mantle cell, 5 extranodal marginal zone, and 9 small lymphocytic [SLL] lymphomas), 4 FL with incipient/partial lymph node involvement, and 11 reactive lymphoid tissues were examined using immunohistochemistry for total and phosphorylated 4E-BP1. Staining intensity was graded as from 0 to 3+. Western immunoblotting (WB) was performed on lysates of 5 mature BCLs (2 FL, 3 DLBCL) and 2 reactive lymph nodal tissues for eIF-4G (total), eIF-4E and 4E-BP1 (total and phosphorylated) expression. In reactive lymphoid tissues, there was regional and cellular specificity of expression of 4E-BP1, with either lack of, or minimal (0 to 1+) cytoplasmic expression in follicular center cells and paracortical T-cells, 2+ expression in follicular dendritic cells and paracortical zone Langerhan cells, and 3+ expression in mantle and marginal zones. p4E-BP1 expression was inverted, with 3+ cytoplasmic immunoreactivity in reactive follicular center cells and no expression in the mantle and marginal zone cells or T-cells, and 2+ or 3+ immunoreactivity in follicular dendritic cells and paracortical zone Langerhan cells. In BCLs, a consistently high level (2+ or 3+) of cytoplasmic 4E-BP1 expression was seen in neoplastic lymphocytes in 45/46 (98%) cases. In contrast, p4E-BP1 was moderately or strongly expressed in 19/46 (41%) cases of BCL, being negative in 17 (37%) cases, and only dimly expressed in the remaining 10 (22%) cases. Three of 4 cases with incipient/partial involvement by FL were easily distinguishable from reactive germinal centers by strong, diffuse staining with 4E-BP1 (and 1+ staining in the 4th case) in neoplastic follicles, distinct from negative/weak staining of adjacent reactive germinal centers. In SLL, slightly higher 4E-BP1 expression was noted in proliferation centers in comparison to surrounding small mature lymphocytes. WB confirmed that non-phosphorylated and p4E-BP1 were expressed in reactive nodes, FL and DLBCL. Other components of the eIF-4F complex including eIF-4G, total and p-eIF-4E and total 4E-BP1 were detectable in whole tissue lysates from BCL samples. We conclude that (a) while 4E-BP1 is almost uniformly expressed in various subtypes of BCL, its level of phosphorylation (indicative of activity) varies widely and has regional and cellular specificity, and (b) 4E-BP1 expression may identify minimal/early lymphomatous involvement in tissues. We speculate that 4E-BP1 phosphorylation may influence the biological behavior of BCLs, since in other investigations we found that the level of phosphorylation of 4E-BP1 correlates with survival after CHOP-based chemotherapy in DLBCL. Our findings support therapeutic trials targeting the eIF-4E pathway in many BCL subtypes, particularly in patients where immunostaining identifies high levels of 4E-BP1 phosphorylation. Disclosures: No relevant conflicts of interest to declare.

scholarly journals CHARACTERIZATION OF SPLENIC LYMPHOID CELLS IN FETAL AND NEWBORN MICE

1973 ◽  
Vol 138 (3) ◽  
pp. 557-573 ◽  
Author(s):  
Patricia G. Spear ◽  
Ai-Lan Wang ◽  
Urs Rutishauser ◽  
Gerald M. Edelman
Keyword(s):  
T Cells ◽  
B Cells ◽  
B Cell ◽  
Cellular Proliferation ◽  
Immunological Response ◽  
Qualitative Change ◽  
Lymphoid Cells ◽  
Antigen Binding ◽  
Newborn Mice ◽  
Quantitative Changes

In order to clarify the cellular events that precede the onset of immunological competence in the mouse, we have characterized and quantitated the lymphoid cells of the spleen as a function of age. Our results show that T cells and B cells both appeared in the spleens of Swiss-L mice as early as the 15th-16th day of gestation. Antigen-binding cells specific for each of three different antigens were also first detected during this same 24 h interval. The B cells and three varieties of antigen-binding cells increased in number rapidly and in parallel until about 1 wk after birth. The T cells, which were more numerous than B cells at first, increased in number somewhat more slowly. Coincident with the onset of response to antigen, there was a further increase in B cell numbers and a decrease in the T cell to B cell ratio. The capacity to respond to antigen by cellular proliferation and synthesis of antibody did not arise until about 2 wk after birth although there were no quantitative changes in the total numbers of T cells, B cells, and antigen-binding cells between 1 and 2 wk of age. Some qualitative change, such as the functional maturation of an antigen-reactive cell, may be required during this interval for the onset of this immunological response. Although the numbers of antigen-binding cells present in fetuses and young animals were smaller than in adults, we have as yet been unable to detect any restriction in the variety of specificities that can be expressed in fetuses, either in the kinds of antigens bound or in the range of avidities with which a single antigen is bound.

Sign in / Sign up

Export Citation Format

Share Document