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Results for “Marginal zone B cells”

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At least 19 recordsLinked to original sources
PubMed1990

Characterization of two monoclonal antibodies (UCL4D12 and UCL3D3) that discriminate between human mantle zone and marginal zone B cells.

Two new monoclonal antibodies (MoAbs), UCL3D3 and UCL4D12 were obtained following immunization with follicular lymphoma (UCL3D3) or low-grade primary B cell gastric lymphoma cells (UCL4D12). In normal splenic white pulp, tonsil and small intestinal Peyer's patches, UCL4D12 recognizes marginal zone B cells and a subpopulation of follicle centre cells, whereas mantle zone B cells are UCL4D12 negative. In contrast, UCL3D3 recognizes mantle zone B cells and follicular dendritic cells, but not marginal zone B cells or follicle centre B cells. Double-immunofluorescence studies showed that in the splenic white pulp, these antibodies stain reciprocally. The majority of UCL3D3+ cells are sIgM+ and sIgD+ whereas a higher proportion of UCL4D12+ cells express surface IgM (sIgM) but not surface IgD (sIgD). Less than 10% of splenic B cells express both 3D3 and 4D12 antigens. None of the cell lines tested expressed either antigen. Functional studies showed that both antigens play a role in B cell activation as the MoAbs increase the mitogenic effect of Staphylococcus aureus Cowan I on tonsil B cells. This effect was maximal at 72 h in culture. TPA activation was reduced, and no effect was observed with anti-immunoglobulin (anti mu) or CDw40 (G28.5). UCL3D3 and UCL4D12 did not show any stimulatory effect on their own. Biochemical studies show that both MoAbs recognize proteins of 80-90 kD under reducing conditions. These two MoAbs appear to recognize new B cell surface antigens which may be useful for identifying subpopulations of B cells.

Animals↗
PubMed1985

Phenotypic expression of B lymphocytes. III. Marginal zone B cells in the spleen are characterized by the expression of Tac and alkaline phosphatase.

The marginal zone of the spleen contains lymphocytes with an intermediate morphologic form between small lymphocytes and plasmablasts. The majority of cells can be stained by B cell monoclonal antibodies including B1, Leu-14, and Leu-12. The most significant finding is the expression of an interleukin 2 receptor (Tac) and an enzyme-alkaline phosphatase by the marginal zone B lymphocytes. The Tac antigen is not normally present in B cells, but can be found in a portion of in vitro-activated B lymphocytes. In conjunction with other evidence, the marginal zone B lymphocytes may represent the activated B cells in the early stages of B cells differentiation. Alternatively, the Tac-positive, marginal zone B lymphocytes may be a discrete subpopulation of activated B cells.

Alkaline Phosphatase↗
PubMed2025

Identification of marginal zone B cells in head and neck cancer with immunomodulatory characteristics.

INTRODUCTION: Recently we observed high numbers of marginal zone B cells (MZBs) within murine head and neck squamous cell carcinoma (HNSCC) with immunosuppressive potential. To date, MZBs have not been linked to tumor development or tumor prevention. OBJECTIVES: Based on our previous findings the present study aimed to validate the presence of MZB in HNSCC and to investigate their possible implications in tumorigenesis and prognosis. METHODS: Flow cytometry was used to uncover MZB within tumors and blood of HNSCC patients. A single-cell RNA sequencing cohort of 118 HNSCC patients across different disease stages and 6 healthy donors (HDs) was compiled. Comparative transcriptomic profiling of B lymphocytes between HNSCC and HDs were performed. Downstream analysis, such as pathway enrichment, cell-cell communication, pseudotime trajectory inference, survival correlation, and spatial transcriptomics were applied. RESULTS: Two MZB subsets were revealed in tissues and blood of HNSCC patients and HDs. The tumor-associated MZBs were featured with hypoxia stress and viral-related hallmark genes. MZB-2, characterized by elevated expression of activation markers and immune-regulatory genes, displayed strong interactions with CD4+ T cells and antigen-presenting cells. These interactions were supported by costimulatory signals in HDs but were absent in HNSCC patients. Co-localization of MZB-2, germinal center B cell (GCB), and CD4+ follicular helper T cell (Tfh) was detected in HNSCC, suggesting the presence of an intratumoral MZB-Tfh-GCB axis. Clinically, MZB-2 abundance was associated with favorable prognosis in early-stage HNSCC, but not in advanced disease. Immunosuppressive gene signatures were not exclusive to MZBs, indicating that they do not represent a purely regulatory B cell phenotype. CONCLUSION: Our findings demonstrate an immunomodulatory role of MZBs in tumor immunity, balancing antigen presentation, cytokine signaling, and immune suppression. The association of MZB-2 with improved prognosis in early-stage HNSCC highlights its potential as a beneficial regulator of antitumor immunity during early tumor progression.

Humans↗
PubMed1989

Human marginal zone B cells are not an activated B cell subset: strong expression of CD21 as a putative mediator for rapid B cell activation.

In the human spleen the marginal zone (MZ) contains medium-sized B cells with a distinct immunophenotype. A main function attributed to the MZ is its involvement in the primary response to blood-borne antigens, in particular to thymus-independent antigens type 2. In this study the presence of antigens related to activation and proliferation was evaluated in human spleens by immunohistochemical staining. It appeared that MZ B cells do not show interleukin 2 receptor expression, and are in G0 phase of the cell cycle, as demonstrated by the lack of Ki-67 reactivity. The most interesting finding is the high CD21 expression by MZ B cells in the absence of IgD expression. As the CD21 antigen has been shown to be involved in B cell activation in close linkage with IgM, it can be suggested that MZ B cells are particularly well equipped for rapid and easy activation in a primary immune response.

Antigens, CD↗
PubMed1985

The human gut contains a novel population of B lymphocytes which resemble marginal zone cells.

B cells in normal human Peyer's patches and in primary B cell lymphomas of the stomach have been characterized in terms of their cellular morphology and their reactivity with a panel of monoclonal antibodies. A population of B cells is present in normal and malignant gut-associated lymphoid tissue which is composed of neither mantle zone cells nor germinal centre cells. In Peyer's patches these cells surround the follicles merging with the mantle zone and extending both into the dome region, infiltrating between the epithelial cells and also towards the serosa. They are intermediate in size with irregular nuclear outlines and they resemble the centrocytes in the follicle centre. They are quiescent, expressing C3b- and C3d-receptors and surface IgM but not surface IgD. These centrocytes-like cells which are not seen in the peripheral lymph nodes are identical to the B cells in the marginal zone of the spleen according to all of the criteria employed in this study.

B-Lymphocytes↗
PubMed1986

Germinal centre formation and follicular antigen trapping in the spleen of lethally X-irradiated and reconstituted rats.

In this study, the relationship between germinal centre formation and the follicular trapping of immune complexes in the rat spleen was investigated. Lethally (9 Gy) X-irradiated rats were reconstituted with thoracic duct lymphocytes and subsequently challenged with sheep red blood cells to induce germinal centre formation. Rats were killed at daily intervals from 1 to 8 days after reconstitution and antigenic stimulation. Antigen trapping capacity during this interval was assessed by intravenous injection of HRP-anti-HRP immune complexes, 24 hr before killing of the animals. Germinal centre formation could be observed from Day 4 onwards. The follicular trapping capacity, which had been abolished by the X-irradiation, however, returned 2 days later (i.e. by Day 6). Apparently, in these experiments, early germinal centre formation could occur without an intact follicular trapping mechanism. It was, therefore, concluded that in this transfer system follicular immune complex trapping is not a prerequisite for the induction of de novo germinal centre formation. Previous studies have shown that both follicular dendritic cells and marginal zone B cells may play a role in the follicular antigen trapping mechanism. FDCs, as detectable with mAB MRC OX 2 in immunoperoxidase-stained frozen sections, were present in spleens at any time after irradiation and reconstitution; the impaired follicular trapping of HRP-anti-HRP immune complexes was therefore not due to an absence of FDCs. Marginal zone B cells, however, were almost absent until 5 days after reconstitution, as observed by immunohistochemical staining with anti-B cell mABs (HIS 14 and HIS 22) and a polyclonal anti-IgD antiserum. Our data suggest that regeneration of follicular antigen trapping capacity is dependent on the presence of marginal zone B cells.

Animals↗
PubMed1992

Cells in the marginal zone of the spleen.

The marginal zone of the spleen forms an intriguing area in which a variety of cell types are combined. Several of these cell types seem to have a fixed position in the marginal zone, such as the marginal zone macrophages, the marginal metallophilic macrophages at the inner border, and, to a lesser extent, the marginal zone B cells. For other cell types--T lymphocytes, small B cells, and dendritic cells--the marginal zone is only a temporary residence. It is this combination of relatively sessile cell populations and the continuous influx and passing of bloodborne immunocompetent cells that turn the marginal zone into a dynamic area, particularly apt for antigen processing and recognition. In no other lymphoid organ can such a unique combination of cells and functions be found. The opening of the arterial blood stream in the marginal sinuses results in a reduction of the velocity of the blood stream, and antigens are initially screened in the marginal zone. To this, extremely potent phagocytic cells, the marginal zone macrophages, are present which can take up and phagocytize large foreign particles, such as bacteria and effete red blood cells. Further filtration of the blood takes place in the filtration beds of the red pulp. The marginal zone macrophages express membrane receptors for bacterial polysaccharides which lead to efficient phagocytosis, probably even in the absence of prior opsonization. Antigenic fragments produced this way can be taken up by dendritic cells that enter the spleen by the blood as part of a mobile surveillance immune system. Dendritic cells present antigen to T cells in the outer area of the T cell-dependent PALS, leading to clustering and enrichment of antigen-specific T cells. Antigens in the marginal zone can also directly associate with memory B cells thought to reside here for longer times, having intimate contact with the marginal zone macrophages. B memory cells then migrate into the PALS and present antigen to T cells. The marginal zone therefore functions not only as an area of initial filtration and phagocytosis of antigens from the blood, but also as a site of lymphocyte emigration. Some of the incoming T and B lymphocytes in the recirculating pool enter the white pulp from the marginal zone. The underlying force and selective molecular mechanisms that guide this migration are unknown. Both B and T lymphocytes recirculate through the outer PALS area on their way to the follicles and the inner PALS, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1988

Memory B cells in T cell-dependent antibody responses colonize the splenic marginal zones.

Specific hapten-binding B cells were identified in the splenic marginal zones following immunization with hapten-protein conjugates. Hapten binding by marginal zone B cells does not appear to be due to passive absorption of anti-hapten antibody. For double immunization with two haptens, 2,4-dinitrophenyl (DNP) and 2-phenyloxazalone (Ox) each conjugated to hemocyanin, resulting in the appearance of discrete DNP-binding cells and Ox-binding cells in the marginal zone. Very few cells were identified which bound both haptens. The hapten-binding cells in the marginal zones have a phenotype characteristic of other marginal zone B cells. They express surface IgM but not IgD. Occasional cells also have surface IgG2c. All hapten-binding cells possessed the antigen recognized by the monoclonal antibody HIS 14 but lacked those identified by HIS24 and HIS22. Hapten-binding B cells were shown to have been in cell cycle shortly before entering the marginal zone but were no longer in cell cycle after arriving at that site. Once in the marginal zone hapten-binding cells were shown to remain in that site for upwards of 2 weeks. Following reimmunization with DNP-hemocyanin, DNP-binding but not Ox-binding cells were lost from the marginal zone. At the same time DNP-binding cells arrived in the periarteriolar lymphocytic sheath and to a lesser extent the follicles. These cells were in active cycle and appeared to give rise both to plasma cells and marginal zone hapten-binding cells. It is concluded that hapten-binding cells found in the marginal zones are memory B cells i.e. they have been derived from B cells which have undergone antigen-driven proliferation, they are no longer in cell cycle but can be induced to re-enter cell cycle by subsequent exposure to antigen. Good antibody responses were obtained following immunization with hapten-polysaccharides; however, no hapten-binding cells appeared in the marginal zones in response to these T cell-independent type 2 antigens.

Animals↗
PubMed1989

Immaturity of the human splenic marginal zone in infancy. Possible contribution to the deficient infant immune response.

The immune response to polysaccharide Ag as present in the capsule of certain virulent bacteria has been demonstrated to be related to a functionally intact spleen. This immune response is almost completely defective in infancy. Because of this the development of cellular compartments in the human spleen was studied immunohistologically in frozen and paraffin tissue sections of 32 infant spleens (less than 2 y of age) and 6 spleens from children. Six cases of sudden infant death syndrome and 7 cases of infection or sepsis which were included showed no significant differences compared to the other cases. Whereas all other cellular compartments have completed their maturation to an adult-type immunophenotype and morphology within the first 5 mo, the infant marginal zone B cells show essentially different features compared to the adult situation. The main characteristics of the infant marginal zone B cells are the absence of CD21-(C3d/EBV-R) expression and the high percentage of cells strongly coexpressing IgM and IgD. As the marginal zone is supposed to be the site of the initiation of the immune response to polysaccharide Ag, there is a remarkable coincidence between the first appearance of MZ B cells with adult features, and the time of acquisition of the ability to mount an immune response to polysaccharides, including encapsulated bacteria.

Adolescent↗
PubMed1992

Human tonsil intraepithelial B cells: a marginal zone-related subpopulation.

AIMS: To determine if intraepithelial B cells in reactive human palatine tonsils were similar to the marginal zone cells of the spleen and Peyer's patches. METHODS: Reactive human palatine tonsils were studied using conventional methods of light microscopy, electron microscopy, and a panel of monoclonal antibodies for leucocyte common antigens. RESULTS: Clinically important numbers of marginal zone-related B cells around the mantle zone were absent in lymphoid follicles, but in the cryptal epithelium there were abundant lymphoid cells with centrocyte-like nuclei and clear cytoplasm, intermingled with macrophages and plasma cells. The immunophenotype of these intraepithelial B cells was distinctive and similar to that found in the splenic marginal zone cells (IgM+, IgD-, CD23-, CD10-, CD35+, CD21+, bc12+, KB61+). CONCLUSIONS: Intraepithelial B cells in human tonsil could represent the counterpart of the marginal zone described in Peyer's patches. Their presence within the epithelium could reflect the destination for the malignant B cells in the lymphoepithelial lesion of mucosa associated lymphoid tissue (MALT) lymphomas. Human palatine tonsil lymphoid tissue has morphological, immunophenotypic, and pathological features similar to those of MALT.

B-Lymphocytes↗
PubMed1991

Tissue distribution of restricted leukocyte common antigens. A comprehensive study with protein- and carbohydrate-specific CD45R antibodies.

A panel of monoclonal antibodies, specific for either protein or carbohydrate components of the leukocyte common antigen (LCA), were used to characterize the expression pattern of different variants of this antigen complex. Immunohistochemical and flow cytometric analysis was carried out on human lymphoid tissues from different anatomical compartments. We found that variations in terminal sialic acid or O-linked sugar moieties were associated with drastic differences in reactivity with some of the CD45R antibodies. For example, the carbohydrate determinants recognized by MT2 (CD45RA) and 2B11 (CD45) were not or were very weakly expressed on germinal center cells, whereas the carbohydrate determinant recognized by MT3 (CD45RB) was not expressed on the majority of mantle zone B cells. On the other hand, KiB3 (CD45RA) reacted with a protein determinant that is normally only exposed on mantle zone B cells but can be uncovered on marginal zone B cells and the CD45RA-positive T-cell subpopulation by enzymatic treatment. The findings suggest that differential biosynthesis and expression of the carbohydrate components of LCA are important mechanisms to generate additional LCA heterogeneity. Similar to the differential usage of the variable region, the exact carbohydrate composition is also linked to the stage of cell development. Heterogeneity in carbohydrate composition of the extracellular domain of LCA appears to enable interactions with different ligands, thereby holding the key to the regulation of LCA cytoplasmic tyrosine phosphatase activity.

Antibodies↗
PubMed1986

Antigen-driven selection of virgin and memory B cells.

This review has summarized the evidence indicating that far more B cells are produced in adult bone marrow than are required to maintain B cell numbers in the periphery. It is shown that most if not all these newly-formed B cells have the potential to become mature peripheral B cells. However, to do this they need to receive an appropriate signal in secondary lymphoid organs. Cells failing to receive such a signal die after a brief period. Two separate situations have been identified which result in recruitment of newly-formed virgin B cells into the peripheral B-cell pool: Following activation by antigen. When the peripheral B-cell pool has been depleted. It is proposed that the first of these signals requires T help and is initiated by antigen presented on interdigitating cells in extrafollicular areas of secondary lymphoid organs. This process seems to be confined to periods immediately following administration of antigen and does not continue in established immune responses to thymus-dependent antigens. It seems probable that continued B cell activation, occurring during long term antibody responses, takes place in the follicles of secondary lymphoid organs and is driven by antigen presented on follicular dendritic cells. Indirect evidence is cited which suggests that somatic mutation in rearranged immunoglobulin V-region genes occurs mainly following B-cell activation in follicles and not during primary B lymphopoiesis. It is suggested that this may involve a hypermutation process which is switched on in activated B cells in germinal centers. Evidence is presented suggesting that plasma cells generated from B cells activated early in immune responses have an average life-span of less than 3 d. However, plasma cells generated in established responses appear to have an average life-span in excess of 20 d. Later sections in the review consider how B-cell recruitment in thymus-independent antibody responses differs markedly from recruitment during thymus-dependent responses. The possible role of splenic marginal zone B cells in some thymus-independent antibody responses is discussed and the evidence indicating that SIgM + ve, IgD-ve marginal zone B cells develop as a distinct population from recirculating SIgM + ve, IgD + ve B cells is summarized.

Adult↗
PubMed1990

A study of the properties of a low-grade mucosal B-cell lymphoma using a monoclonal antibody specific for the tumour immunoglobulin.

Primary low-grade B-cell lymphomas of mucosa-associated lymphoid tissue (MALT) are tumours with distinctive clinico-pathological characteristics, two of which are studied in this paper, namely the tendency of the tumours to remain localized and the morphologic and phenotypic resemblance of the malignant cells to splenic marginal zone B cells. We have made a detailed study of a small intestinal lymphoma and a gastric lymphoma, which together with the spleen were resected from the same patient. Using a monoclonal antibody (7G3) raised against a unique determinant on the small intestinal tumour, we were able to detect disseminated small intestinal tumour cells in the stomach and spleen. The tumour in the stomach was genetically related, but non-identical to that in the small intestine, and was not recognized by 7G3. Lymphocytes expressing the marker of the small intestinal tumour (7G3) were present in lymphoid nodules in the stomach, and 7G3+ plasma cells were present beneath the gastric epithelium. In the spleen, cells expressing 7G3 were present in the marginal zone and plasma cells expressing the same marker were present in the red pulp. These findings suggest that low-grade MALT lymphomas may migrate beyond the primary tumour site, but that tumour cells distant to the primary site may differentiate into mature, non-dividing plasma cells. The localization of small intestinal tumour cells in the splenic marginal zones reinforces the suggestion of lineage homology between these populations of cells.

Antibodies, Monoclonal↗
PubMed1976

T- and B-areas in immune reactions. Volume changes in T and B cell compartments of the rat spleen following intravenous administration of a thymus-dependent (SRBC) and a thymus-independent (paratyphoid vaccin-endotoxin) antigen. A histometric study.

In the white pulp of rat spleens cell numbers were studied in the different compartments following intravenous administration of comparable doses of paratyphoid vaccine (PTV, thymus-independent) and sheep red blood cells (SRBC, thymus-dependent). In the periarteriolar lymphatic sheaths (PALS) both cell concentration and volume were measured. For the follicles and the marginal zone only volume was recorded in the first 5 days following antigen administration. Additionally, histologic observations were made. In the thymus-dependent area PTV caused oedema 12-24 hours after administration. Following SRBC administration an increase in lymphocyte numbers occurred until the second day, probably representing an influx of T cells from the recirculating pool. Both antigens gave rise to a plasmacellular reaction in the peripheral PALS (2nd-4th day). In the bone marrow-dependent areas a massive shift of medium-sized lymphocytes from the marginal zone to the follicles took place in the first 24 hours following PTV administration. These cells subsequently transformed into blasts. After SRBC (6 and 12 hours) only a few marginal zone lymphocytes seemed to migrate into the follicles. It is aruged that the endotoxin present in PTV is responsible for the fact that, following administration of the antigen, all marginal zone (B) cells responded. Endotoxin stimulation might provide a model for the fate of marginal zone cells stimulated by other agents, such as antigen (stimulating antigen binding B cells) or antigen-antibody complexes (stimulating Fc-receptor B cells).

Animals↗