A novel in vivo follicular dendritic cell-dependent iccosome-mediated mechanism for delivery of antigen to antigen-processing cells

Recent scanning electron microscopic studies on isolated follicular dendritic cells (FDC) showed that dendrites of certain FDC were "beaded," i.e., consisting of a series of interconnected immune complex coated bodies (termed "iccosomes," measuring 0.3 to 0.7 micron diameter). In vitro these iccosomes detach from one another with ease. The major objectives herein were to establish whether these structures can be detected in sections and whether iccosomes serve to disseminate antigen in vivo. Beginning at day 1, the time point used for isolating beaded FDC, the popliteal lymph nodes of immune C3H mice were studied with light and transmission electron microscopy for 2 wk (i.e., at days 1, 3, 5, 8, and 14) after hind footpad injection of the histochemically detectable antigen, horseradish peroxidase (HRP). Iccosomes (0.25 to 0.38 micron diameter), contoured by a peroxidase (PO)-positive coat of HRP-anti-HRP complexes, were first detected by transmission electron microscopy at day 1 adjacent to cell bodies of certain FDC. Within their limiting membrane they contained flocculent material that was PO positive. At day 3 by light microscopy, germinal centers were seen enlarged and the antigen-retaining reticulum, composed of antigen-bearing FDC, appeared diffuse. This coincided with the transmission electron microscopic visualization of a dispersed state of iccosomes among the follicular lymphocytes. At that time iccosomes were seen attached to the surface of lymphocytes via PO-positive immune complexes and were surrounded by microvillous processes of these cells. Germinal center lymphocytes and tingible body macrophages both responded to contact with iccosomes by endocytosis. Antigen-containing tingible body macrophage were most conspicuous by light microscopy at day 5, when transmission electron microscopy showed that the majority of germinal center lymphocytes contained endocytosed HRP in secondary lysosome-like granules associated with the Golgi apparatus. The number of dispersed iccosomes was markedly reduced by day 5. In controls injected with HSA, a PO-negative antigen, lymphocytes and tingible body macrophages were PO-negative. The presence of antigen in both cell types was confirmed through the use of a gold-conjugated antigen (goat IgG). Simultaneous immunoperoxidase labeling of the same tissues with anti-Ia showed the gold conjugate containing B cells to be Ia+. Antigen-positive B cells and tingible body macrophages were greatly reduced in numbers by day 14, suggesting the intracellular fragmentation of the antigen.(ABSTRACT TRUNCATED AT 400 WORDS)     

The function and origin of follicular dendritic cells

Follicular dendritic cells (dendritic reticular cells) in germinal centres bind antigen-antibody complexes via C3 receptors and retain the complexes at their surface for long periods of time. The follicular dendritic cells (FDC) are distinct from macrophages and from dendritic cells found in T-dependent areas, and are not derived from bone marrow stem cells. On histological evidence it has been proposed that they are derived from reticulum cells. Complexes are probably transported to FDC by a subpopulation of B cells in the marginal zone. Binding of complexes to FDC causes germinal centre enlargement and is a very efficient, and possibly essential stimulus to the generation of B memory cells which recognize epitopes on antigen or antibody in the complexes. An hypothesis is discussed which draws together these observations and suggests that antigen on FDC plays a central role in control of humoral immunity.     

Follicular dendritic cells in suspension: identification, enrichment, and initial characterization indicating immune complex trapping and lack of adherence and phagocytic activity

Antigen-retaining follicular dendritic cells (FDC) have been identified and studied in sections of lymph nodes and spleen, but studies of these cells in culture have been extremely limited. The purpose of this study was to establish techniques to release these fragile cells from mouse lymph nodes in a viable state and to identify these cells routinely in lymph node cell suspensions. FDC were obtained from passively or actively immunized popliteal lymph nodes of mice injected in the footpads with 125I-labeled human serum albumin (HSA) or horseradish peroxidase (HRP). Lymph nodes were removed 1 hr after the footpads had been injected with collagenase. After another hour of incubation in vitro with collagenase, protease, and deoxyribonuclease, FDC were released by gentle teasing and enriched by centrifugation on a low density bovine serum albumin (BSA) or Percoll gradient. Most FDC with the associated radiolabel floated at densities greater than 1.06 g/ml on BSA or Percoll gradients. Slides of the FDC-enriched fraction were prepared, using a cytobucket which allowed the cells to be affixed to glass slides by centrifugation in a less disruptive manner than by cytocentrifugation. FDC that were air-dried and fixed with 3% glutaraldehyde had a characteristic pink acidophilic cytoplasm after Wright's staining, and had a faintly basophilic euchromatic nucleus frequently with peripherally-clumped chromatin. In addition, these cells were large and irregularly shaped (up to 60 micron long). Fixation of FDC with 0.6% paraformaldehyde/ 0.9% glutaraldehyde on poly-L-lysine-coated slides resulted in a preservation of FDC which made possible visualization of long dendritic processes by Nomarski optics. Antigen presence on the cell surface was confirmed by autoradiography and, in the case of HRP, was also visualized enzymatically using diaminobenzidine. In contrast to resident peritoneal macrophages or some contaminating lymph node macrophages present on the same slides, FDC did not phagocytize opsonized sheep red blood cells (SRBC) or adhere to plastic surfaces although they did form rosettes with opsonized SRBC. Cell marker studies indicated FDC have a distinctive phenotype. They were positive for Ia, Fc receptor, and leukocyte common antigen, but negative for Thy-1, Ly-1, Ly-2, endogenous Ig, Mac-1, Mac-2, Mac-3, and F4/80, and negative to weakly positive for nonspecific esterase. Cultured FDC remained viable and retained radiolabeled antigen-antibody complexes on their surfaces and were significantly enriched for FDC.(ABSTRACT TRUNCATED AT 400 WORDS)     

FDC-SP,a novel secreted protein expressed by follicular dendritic cells

To define better the molecular basis for follicular dendritic cell (FDC) function, we used PCR-based cDNA subtraction to identify genes specifically expressed in primary FDC isolated from human tonsils. In this work we report the discovery of a novel gene encoding a small secreted protein, which we term FDC-SP (FDC secreted protein). The FDC-SP gene lies on chromosome 4q13 adjacent to clusters of proline-rich salivary peptides and C-X-C chemokines. Human and mouse FDC-SP proteins are structurally unique and contain a conserved N-terminal charged region adjacent to the leader peptide. FDC-SP has a very restricted tissue distribution and is expressed by activated FDCs from tonsils and TNF-alpha-activated FDC-like cell lines, but not by B cell lines, primary germinal center B cells, or anti-CD40 plus IL-4-activated B cells. Strikingly, FDC-SP is highly expressed in germinal center light zone, a pattern consistent with expression by FDC. In addition, FDC-SP is expressed in leukocyte-infiltrated tonsil crypts and by LPS- or Staphylococcus aureus Cowan strain 1-activated leukocytes, suggesting that FDC-SP can also be produced in response to innate immunity signals. We provide evidence that FDC-SP is posttranslationally modified and secreted and can bind to the surface of B lymphoma cells, but not T lymphoma cells, consistent with a function as a secreted mediator acting upon B cells. Furthermore, we find that binding of FDC-SP to primary human B cells is markedly enhanced upon activation with the T-dependent activation signals such as anti-CD40 plus IL-4. Together our data identify FDC-SP as a unique secreted peptide with a distinctive expression pattern within the immune system and the ability to specifically bind to activated B cells.     

Interneurons: an electron microscopic study of the cat's hippocampal formation, II.

The ultrastructure of interneurons was studied in the cat and it was found to differ from that of the pyramidal and granule cells. The size, shape and topographic situation of the cell body of interneurons were the criteria for approaching their identification with the cells found in Golgi material. Some interneuron dendrites are also described. The varicose and spindle-shaped dendritic profiles belonging to interneurons are different in size. In Golgi material the interneurons have beaded (varicose) or spindle-shaped dendrites. The arrangement of synaptic terminals on the interneuron dendritic surface seems to be their characteristic feature.     

Transport of immune complexes from the subcapsular sinus to lymph node follicles on the surface of nonphagocytic cells, including cells with dendritic morphology

The objective of the present study was to investigate the mechanism of antigen migration from the site of initial localization in the lymph node subcapsular sinus (SS) to regions of follicular retention in the cortex. The migration of horseradish peroxidase (HRP), used as a histochemically identifiable antigen, was followed by light and electron microscopy in C3H mouse popliteal lymph nodes obtained 1, 5, 15, and 30 min, and 5 and 24 hr after hindfoot pad injection of HRP. The observations showed that as early as 1 min after HRP injection, localization of antigen occurred at distinct sites in the SS and subjacent areas of the cortex on the afferent side. At these sites, between 1 min and 24 hr, the antigen formed light microscopically identifiable trails, which reached progressively deeper into the cortex with time toward individual follicular regions. By 24 hr this apparent migration of antigen was complete, and HRP was localized in follicles. This migration pattern did not occur on the efferent sides of lymph nodes, and it was dependent on the systemic presence of specific antibodies since it was observable only in passively immunized but not in nonimmune mice. Temporary retention of antigen by typical macrophages was also observed in the SS on the efferent side. This was minimal in nonimmune mice and was significantly enhanced in passively immunized mice. Electron microscopy indicated that the apparent migration of immune complexes was mediated by a group of cells observed in the migration path that had immune complexes sequestered on their surface or in plasma membrane infoldings. These antigen transporting cells (ATC) were relatively large nonphagocytic cells, with lobated or irregular euchromatic nuclei and cell processes of various complexity. ATC observed in or near the SS appeared to be less differentiated, were monocyte-like, and resembled non-Birbeck granule-containing Langerhans cell precursors or veiled cells. Others, located deeper in the cortex, appeared more differentiated, interdigitated with antigen-retaining dendritic cells, and shared morphologic characteristics with follicular dendritic cells (FDC). The results support the concepts that immune complexes are trapped in the SS and are transported by a group of non-phagocytic cells, other than lymphocytes, to follicular regions. The mechanism of transport may involve the migration of ATC with a concomitant maturation into FDC, or by a mechanism of ATC to FDC transport utilizing dendritic cell processes and membrane fluidity, or by a combination of the two mechanisms.     

The morphology and topographic distribution of AII amacrine cells in the cat retina

When cat retina is incubated in vitro with the fluorescent dye, 4',6-diamidino-2-phenyl-indole (DAPI), a uniform population of neurons is brightly labelled at the inner border of the inner nuclear layer. The dendritic morphology of the DAPI-labelled cells was defined by iontophoretic injection of Lucifer yellow under direct microscopic control: all the filled cells had the narrow-field bistratified morphology that is distinctive of the AII amacrine cells previously described from Golgi-stained retinae. Although the AII amacrines are principal interneurons in the rod-signal pathway, their density distribution does not follow the topography of the rod receptors, but peaks in the central area like the cone receptors and the ganglion cells. There are some 512 000 AII amacrines in the cat retina and their density ranges from 500 cells per square millimetre at the superior margin to 5300 cells per square millimetre in the centre (retinal area is 450 mm2). The isodensity contours are kite-shaped, particularly at intermediate densities, with a horizontal elongation towards nasal retina. The cell body size and the dendritic dimensions of AII amacrines increase with decreasing cell density. The lobular dendrites in sublamina a of the inner plexiform layer span a restricted field of 16-45 microns diameter, while the arboreal dendrites in sublamina b form a varicose tree of 18-95 microns diameter. The dendritic field coverage of the lobular appendages is close to 1.0 (+/- 0.2) at all eccentricities whereas the coverage of the arboreal dendrites doubles within the first 1.5 mm and then remains constant at 3.8 (+/- 0.7) throughout the periphery.     

猫视网膜多巴胺能神经元的形态和发育

Morphology and development of dopaminergic neurons has been studied in the kitten retina, using tyrosine hydroxylase (TH) immunocytochemistry. TH immunoreactive (TH+) cells are already presented in whole amount and sectioned retina at first postnatal day (P1). According to soma size, shape, dendritic process pattern and immunoreactivity, two classes, type I or large dark staining TH+ cells and type II or small light staining TH+ cells are recognized. The TH I cells which consisting of normal placed DA amacrine cells, displaced DA amacrine cells and DA interplex-form-like cells, gradually mature during postnatal development, while TH II cells decrease quickly and through disappear at P30. After eye opening TH I amacrine cells, especially their dendrites develop quickly. The soma diameters increase from 11.8 microns (P1) to 14.2 microns (P30). The dendritic fields increase in size and complexity. At P1 the thick radiating dendrites emerge from the cell body with small or large "spines" and many growth cones. At P13 the dendritic field is markedly enlarged and only a few growth cones can be seen on some stained dendrites. In addition, the dendritic spines are no longer apparent and they are a part of rudimentary rings. By P30 the dendritic plexus of TH+ dendrites and rings in the out most part of IPL, typical of the adult cells, are complete. The influence of light on the development of DA cells after eye opening and the possibility of neurotransmitter changing are discussed.     

Fine structure of the stretch receptor in the bursa copulatrix of the butterfly,Pieris rapae crucivora

Summary A pair of multipolar stretch-receptive neurons were found in the bursa copulatrix of the female cabbage white butterfly, Pieris rapae crucivora. The cell body of each neuron, about 10 m in diameter, lies on the edge of the muscular region in the antero-lateral wall of the corpus bursae. No special accessory structure, such as a receptor muscle, is associated with the neuron. The several dendrites extend radially into the muscle layer. The dendrites are ensheathed except for their terminal tips, and, on their course, they anchor repeatedly on the epithelial cells or the muscle fibers in such a manner that their basement membranes fuse together. While the ensheathed dendrite is usually 0.1–0.2 m in diameter, it often forms 1–2 m varicosities especially at anchor sites, so that it looks like a varicose, or beaded, chain. The varicosities contain a number of mitochondria, but only microtubules are found in the fine interconnecting parts of the dendrite. The naked dendritic tips terminate in the basement membrane of the epithelial cell. The varicosities, as well as naked tips, seem to be important for stimulus transduction in the sensory cell of this type.     

Cell types within the medial forebrain bundle: a Golgi study of preoptic and hypothalamic neurons in the rat

The morphology of lateral preoptic (POL) and lateral hypothalamic (HLA) neurons was studied in 14- to 200-day-old rats with the chlorate-formaldehyde modification of the Golgi method. Drawings of 91 POL and HLA neurons revealed three distinct neuronal types within the MFB based on somatic size and shape and dendritic morphology. Class I neurons, which accounted for 75-80% of the neurons in the MFB, has fusiform or multipolar somata averaging 21 X 14 micron and 2-5 sparsely branched dendrites with a moderate number of sticklike spines. The extensive dendritic domains of Class I neurons ranged from 700 to 1,500 micron and were usually oriented perpendicular to the longitudinal fibers of the MFB. Both nonoriented and oriented Class I neurons were encountered. Nonoriented Class I neurons had expansive dendritic arbors which reached nearly all regions of the MFB in the coronal plane. Oriented Class I neurons had dendritic domains which were confined to specific regions (e.g., ventral-lateral) of the MFB. Class II neurons, which made up approximately 10% of the MFB neurons, had large multipolar somata averaging 30 X 17 micron and 2-5 stout dendrites which were densely covered with hairlike spines. Class II neurons also exhibited spines on their somata and proximal dendritic trunks and had dendritic domains of 700-1,000 micron. Class III neurons had small somata averaging 15 X 12 micron and restricted dendritic arbors of 500-700 micron in diameter. Class III neurons exhibited both spiny and spine-free dendrites and made up 10% of MFB neurons. Because of the parcellation of chemically coded fiber systems within the MFB, individual POL and HLA neurons may not be homogeneous in the type of afferents they receive from other brain areas.     

Expression of the intercellular adhesion molecule-1 on high endothelial venules and on non-lymphoid antigen handling cells: interdigitating cells,antigen transporting cells and follicular dendritic cells

Intercellular adhesion molecule-1 (ICAM-1)¹ has been implicated in the development of germinal center reactions in vitro, and the present study was undertaken to determine the distribution of ICAM-1 in active germinal centers in vivo and in murine secondary lymphoid tissues in general. Anti-ICAM-1-specific monoclonal antibodies were used in conjunction with immunohistochemistry at both the light and ultrastructural levels of resolution. Examination of cryostat sections of lymph nodes, spleens, and Peyer's patches revealed that anti-ICAM-1 distinctly labeled cells in the light zones of germinal centers, a few cells in the T cell zones (e.g. paracortex of lymph nodes), cells in the sinus floor of the subcapsular sinuses of lymph nodes, and high endothelial venules (HEV). Ultrastructural studies revealed that the cells labeling with anti-ICAM-1 in germinal centers were follicular dendritic cells (FDC) which appeared to have more ICAM-1 than any other cell type. The surfaces of well-developed, intricate, convoluted FDC processes were intensely labeled even under conditions where B cells appeared negative. Interdigitating cells (IDC) were also labeled as were certain endothelial cells in the HEV. The cells in the subcapsular sinus floor labeling with anti-ICAM-1 were the antigen transporting cells (ATC) that carry antigen-antibody complexes into lymph node follicles. We suspect ATC are FDC precursors which mature into FDC in the follicles. Interestingly, FDC, IDC, and ATC are 3 important accessory cells known to handle antigens in specific compartments of lymphoid tissues. The marked localization of this adhesion molecule on these critical antigen handling cells supports the concept that ICAM-1 is important in providing the intercellular adhesion necessary for optimal initiation of immune responses in vivo.Abbreviations ICAM-1 Intercellular adhesion molecule-1 - LFA-1 leukocyte functional antigen-1 - IDC interdigitating cells - ATC antigen transporting cells - FDC follicular dendritic cells - HEV high endothelial venules - DC dendritic cells - PBS phosphate-buffered saline - PLP periodate-lysine-4% paraformaldehyde - GPLP periodate-lysine-0.1% glutaraldehyde-2% paraformaldehyde - EM electron microscopy - HRP horseradish peroxidase - DAB diaminobenzidine tetrahydrochloride - HSA human serum albumin     

The neurons in layer 1 of cat visual cortex.

We have examined the morphology of neurons in layer 1 by injecting them intracellularly with lucifer yellow in lightly fixed brain slices (250 microns thick) taken from the medial bank of area 17 in adult cats. Of 22 neurons with well-filled dendrites, 16 had smooth dendrites, two had sparsely spiny dendrites (less than 200 spines) and, unexpectedly, four had spiny dendrites typical of pyramidal cells. The axon was generally not well filled. Computer reconstructions showed that parts of the dendritic tree had been lost in the sectioning. Nevertheless, measurements of the length of intact dendrites suggested an average diameter of the dendritic tree of 220 microns. The density of the neurons was such that the dendritic trees of about six neurons cover each point in layer 1. Thus, despite the very low density of neurons that characterizes layer 1, there are more than sufficient neurons to sample from the entire representation of the visual field in area 17.     

Scrapie-specific pathology of sheep lymphoid tissues

Transmissible spongiform encephalopathies (TSEs) or prion diseases often result in accumulation of disease-associated PrP (PrP(d)) in the lymphoreticular system (LRS), specifically in association with follicular dendritic cells (FDCs) and tingible body macrophages (TBMs) of secondary follicles. We studied the effects of sheep scrapie on lymphoid tissue in tonsils and lymph nodes by light and electron microscopy. FDCs of sheep were grouped according to morphology as immature, mature or regressing. Scrapie was associated with FDC dendrite hypertrophy and electron dense deposit or vesicles. PrP(d) was located using immunogold labelling at the plasmalemma of FDC dendrites and, infrequently, mature B cells. Abnormal electron dense deposits surrounding FDC dendrites were identified as immunoglobulins suggesting that excess immune complexes are retained and are indicative of an FDC dysfunction. Within scrapie-affected lymph nodes, macrophages outside the follicle and a proportion of germinal centre TBMs accumulated PrP(d) within endosomes and lysosomes. In addition, TBMs showed PrP(d) in association with the cell membrane, non-coated pits and vesicles, and also with discrete, large and random endoplasmic reticulum networks, which co-localised with ubiquitin. These observations suggest that PrP(d) is internalised via the caveolin-mediated pathway, and causes an abnormal disease-related alteration in endoplasmic reticulum structure. In contrast to current dogma, this study shows that sheep scrapie is associated with cytopathology of germinal centres, which we attribute to abnormal antigen complex trapping by FDCs and abnormal endocytic events in TBMs. The nature of the sub-cellular changes in FDCs and TBMs differs from those of scrapie infected neurones and glial cells suggesting that different PrP(d)/cell membrane interactions occur in different cell types.     

Precise localization of antigens on follicular dendritic cells

Summary Horse-spleen ferritin or bovine serum albumin conjugated to colloidal gold (BSA-gold) were injected subcutaneously in preimmunized mice. In draining lymph nodes both antigens were located in macrophages or between the cytoplasmic processes of follicular dendritic cells (FDC). Some of the antigens remained trapped on FDC until day 31 after injection. Simultaneous injection of both antigens showed that they were located between the infoldings of the same FDC. These cells are thus able to retain at least two different antigens on their surface. The peculiar arrangement of ferritin between the cytoplasmic infoldings suggests that this antigen is fixed on both cell membranes by specific antibodies. The trapped immune complexes could thus stabilize the FDC membrane system.The antigen retention requires the presence of specific antibodies since BSA-gold or ferritin injected without preimmunization were not found between FDC processes. Nonantigenic materials, such as colloidal gold or carbon particles, are not trapped by FDC, except when injected in large amounts.The antigens were trapped on the surface of FDC, however unfrequently in close contact with lymphocytes. FDC might protect lymphocytes against an excess of immune complexes and act as regulators of contacts between lymphocytes and immune complexes.Abbreviations BSA bovine serum albumin - BSA-gold BSA conjugated to colloidal gold particles - FDC follicular dendritic cells     

Gliding movements in Myxococcus xanthus.

Prokaryotic gliding motility is described as the movement of a cell on a solid surface in the direction of the cell's long axis, but its mechanics are unknown. To investigate the basis of gliding, movements of individual Myxococcus xanthus cells were monitored by employing a video microscopy method by which displacements as small as 0.03 micron could be detected and speeds as low as 1 micron/min could be resolved. Single cells were observed to glide with speeds varying between 1 and 20 microns/min. We found that speed variation was due to differences in distance between the moving cell and the nearest cell. Cells separated by less than one cell diameter (0.5 micron) moved with an average speed of 5.0 micron/min, whereas cells separated by more than 0.5 micron glided with an average speed of 3.8 microns/min. The power to glide was found to be carried separately at both ends of a cell.     

Influence of immunoglobulin isotypes and lymphoid cell phenotype on the transfer of immune complexes to follicular dendritic cells

Follicular dendritic cells (FDC) are located only inside lymph follicles and are characterized mainly by their capacity to retain high amounts of immune complexes by their Fc or C3b receptors. In this work, we examine the influence of immunoglobulin isotypes and the subset of lymphoid cells (B or T) upon the transfer of immune complexes from lymphocytes to FDC. FDC isolated from mice lymph nodes by enzymatic digestion are able to fix, through Fc receptors, gold-labeled immune complexes presented by lymphoid cells. As demonstrated by electron microscopy, this transfer requires the establishment of close contacts between both cell types. Using different cell selection techniques we show that B lymphoid cells take up immune complexes more efficiently than do T lymphoid cells and transfer a larger number of them to FDC. This transfer mechanism is dependent on the immunoglobulin isotype: immune complexes constituted of IgG2a, IgG2b, and IgG1 isotypes are better transferred to FDC than those constituted of IgG3 and IgM.     

TC1(C8orf4) is upregulated by IL-1beta/TNF-alpha and enhances proliferation of human follicular dendritic cells

Follicular dendritic cells (FDC) play crucial roles in immune regulation. TNF-alpha has been shown to be essential to the FDC network. However, the molecular regulation of FDC proliferation has not been characterized. Here, we show that TC1(C8orf4), a novel positive regulator of the Wnt/beta-catenin pathway in vertebrates, is upregulated by IL-1beta and TNF-alpha in the human FDC-like line HK. TC1 enhances HK cell proliferation, while TC1-knockdown inhibits the proliferation induced by IL-1beta, suggesting a role of TC1 as a regulator of FDC proliferation. The regulation by pro-inflammatory cytokines suggests that TC1 might be implicated in linking local inflammation to immune response by stimulating FDC.     

Distribution of motor cortical neuron synaptic terminals on monkey parvocellular red nucleus neurons.

We determined the location of 54 horseradish peroxidase (HRP)-labeled motor cortical neuron synaptic terminals on 17 parvocellular neurons in the monkey red nucleus. Synaptic terminals and their postsynaptic elements were identified and reconstructed, using light- and electron-microscopic techniques, from serial thick and thin sections. Terminals were found on proximal and distal dendrites of small and medium-sized parvocellular neurons, where they formed excitatory synapses. Some were 180 microns from cell somata. Approximately half of the labeled terminals, aside from those located at dendritic origins, were situated strategically at or near dendritic branch points. Since monkey parvocellular neurons show little activity during movement, the obvious next question is this: How and in what way does motor cortex influence these cells?     

Regulation of follicular dendritic cell networks by activated T cells: the role of CD137 signaling

B cells, but not T cells, are considered to be important for the formation of follicular dendritic cell (FDC) clusters. Stimulation with agonist mAbs against CD137 (4-1BB), a TNFR family member primarily expressed on activated T cells, was effective in promoting T cell responses, but paradoxically suppressed T-dependent humoral immunity and autoantibody production in autoimmune disease models. Our present study shows that agonistic anti-CD137 treatment activates T cells, resulting in diminished FDC networks in B cell follicles, which are important components in T-dependent humoral immune responses both before and after the initiation of an immune response. Pretreatment with anti-CD137 before the secondary immunization inhibited memory Ab responses. Interestingly, CD137 costimulation-induced diminishment of FDC is T cell dependent. In addition, both CD4(+) and CD8(+) T cells are recruited into FDC area and are able to regulate FDCs by CD137 costimulation through a direct or indirect mechanism. These studies have revealed a previously unappreciated role of T cells in the regulation of FDC networks.