Lysosomal glycosphingolipid recognition by NKT cells

NKT cells represent a distinct lineage of T cells that coexpress a conserved alphabeta T cell receptor (TCR) and natural killer (NK) receptors. Although the TCR of NKT cells is characteristically autoreactive to CD1d, a lipid-presenting molecule, endogenous ligands for these cells have not been identified. We show that a lysosomal glycosphingolipid of previously unknown function, isoglobotrihexosylceramide (iGb3), is recognized both by mouse and human NKT cells. Impaired generation of lysosomal iGb3 in mice lacking beta-hexosaminidase b results in severe NKT cell deficiency, suggesting that this lipid also mediates development of NKT cells in the mouse. We suggest that expression of iGb3 in peripheral tissues may be involved in controlling NKT cell responses to infections and malignancy and in autoimmunity.     

Autophagy-dependent viral recognition by plasmacytoid dendritic cells

Plasmacytoid dendritic cells (pDCs) detect viruses in the acidified endosomes by means of Toll-like receptors (TLRs). Yet, pDC responses to certain single-stranded RNA (ssRNA) viruses occur only after live viral infection. We present evidence here that the recognition of such viruses by TLR7 requires transport of cytosolic viral replication intermediates into the lysosome by the process of autophagy. In addition, autophagy was found to be required for the production of interferon-alpha by pDCs. These results support a key role for autophagy in mediating ssRNA virus detection and interferon-alpha secretion by pDCs and suggest that cytosolic replication intermediates of viruses serve as pathogen signatures recognized by TLR7.     

Supraoptic neurosecretory cells: adrenergic and cholinergic sensitivity

Adrenergic and cholinergic agonists and antagonists were applied microelectrophoretically to over 700 neurons in the cat supraoptic nucleus, 20 percent of which were antidromically identified as neurosecretory cells. Norepinephrine uniformly depressed all sensitive cells. Acetylcholine caused both muscarinic depression and nicotinic excitation which were antagonized by atropine and dihydro-beta-erythroidine, respectively. These results support the hypothesis that norepinephrine and acetylcholine are directly involved in controlling the release of antidiuretic hormone.     

Generation of adrenergic and cholinergic potentials in sympathetic ganglion cells

Norepinephrine elicited a hyperpolarizing response, and acetylcholine (during nicotinic blockade) elicited a depolarizing one. Both responses showed no increase in membrane conductance. The norepinephrine response was suppressed by initial depolarization; the acetylcholine response (frog cells); by hyperpolarization. These neurotransmitters apparently can activate electrogenic mechanisms which do not involve movement of ions down their electrochemical gradients.     

Place cells and place recognition maintained by direct entorhinal-hippocampal circuitry

Place cells in hippocampal area CA1 may receive positional information from the intrahippocampal associative network in area CA3 or directly from the entorhinal cortex. To determine whether direct entorhinal connections support spatial firing and spatial memory, we removed all input from areas CA3 to CA1, thus isolating the CA1 area. Pyramidal cells in the isolated CA1 area developed sharp and stable place fields. Rats with an isolated CA1 area showed normal acquisition of an associative hippocampal-dependent spatial recognition task. Spatial recall was impaired. These results suggest that the hippocampus contains two functionally separable memory circuits: The direct entorhinal-CA1 system is sufficient for recollection-based recognition memory, but recall depends on intact CA3-CA1 connectivity.     

Alloantigen recognition is preceded by nonspecific adhesion of cytotoxic T cells and target cells

T-cell receptors bind antigens only when the antigens are exposed on the cell surface. This can be studied best in the interaction of cytolytic T lymphocytes (CTL) with target cells because the recognition and binding event can be separated from the lytic phase. Studies with CTL clones specific for HLA-A2 and HLA-B7 demonstrated that conjugates of CTL's and target cells can be formed in the absence of specific antigen recognition. Furthermore, T-cell receptor and target antigen cannot interact unless there is conjugate formation. This indicates that nonspecific conjugate formation between CTL's and target cells precedes the recognition of specific antigen by the T-cell receptor.     

Arthritis provoked by linked T and B cell recognition of a glycolytic enzyme

The hallmark of rheumatoid arthritis (RA) is specific destruction of the synovial joints. In a mouse line that spontaneously develops a disorder with many of the features of human RA, disease is initiated by T cell recognition of a ubiquitously expressed self-antigen; once initiated, pathology is driven almost entirely by immunoglobulins. In this study, the target of both the initiating T cells and pathogenic immunoglobulins was identified as glucose-6-phosphate isomerase, a glycolytic enzyme. Thus, some forms of RA or related arthritides may develop by a mechanism fundamentally different from the currently popular paradigm of a joint-specific T cell response.     

Mitotic division in pancreatic beta cells

Successful expansion of the islet cell mass occurs in genetically diabetic mice (C57 Bl/Ks-dbdb) following a period of dietary restriction, in the absence of a population of precursor cells. Differentiated cells that synthesize insulin retain the capability of undergoing mitotic division.     

Generation of gut-homing IgA-secreting B cells by intestinal dendritic cells

Normal intestinal mucosa contains abundant immunoglobulin A (IgA)-secreting cells, which are generated from B cells in gut-associated lymphoid tissues (GALT). We show that dendritic cells (DC) from GALT induce T cell-independent expression of IgA and gut-homing receptors on B cells. GALT-DC-derived retinoic acid (RA) alone conferred gut tropism but could not promote IgA secretion. However, RA potently synergized with GALT-DC-derived interleukin-6 (IL-6) or IL-5 to induce IgA secretion. Consequently, mice deficient in the RA precursor vitamin A lacked IgA-secreting cells in the small intestine. Thus, GALT-DC shape mucosal immunity by modulating B cell migration and effector activity through synergistically acting mediators.     

Extrafollicular activation of lymph node B cells by antigen-bearing dendritic cells

In contrast to na?ve T cells that recognize short antigen-derived peptides displayed by specialized antigen-presenting cells, immunoglobulin receptors of B lymphocytes primarily recognize intact proteins. How and where within a lymph node such unprocessed antigens become available for na?ve B cell recognition is not clear. We used two-photon intravital imaging to show that, after exiting high-endothelial venules and before entry into lymph node follicles, B cells survey locally concentrated dendritic cells. Engagement of the B cell receptor by the dendritic cell (DC)-associated antigen leads to lymphocyte calcium signaling, migration arrest, antigen acquisition, and extrafollicular accumulation. These findings suggest a possible role for antigen-specific B-DC interactions in promoting T cell-dependent antibody responses in vivo.     

uc.12+A在B细胞淋巴瘤中的功能研究

从C57BL/6野生型小鼠骨髓中分选出正常B细胞,应用实时荧光定量PCR (qRT-PCR)检测uc.12+A在小鼠正常B细胞和B淋巴瘤细胞的表达水平.通过分子克隆将uc.12+A基因序列构建到pMSCV-PIG反转录病毒表达载体上,包装成反转录病毒感染小鼠B淋巴瘤细胞38B9和人Burkitt淋巴瘤细胞Romas,经...     

一种字符识别算法在自动识别系统中的应用

光学字符识别是模式识别领域中最经典也是得到最广泛应用的方向之一,而车牌识别系统是应用光学字符识别技术的典型系统。文章基于车牌识别系统的开发,提出一种基于二值图像的字符识别算法。在该算法中,提取字符的点阵特征、特征线和网格特征,分类器采用神经网络。为充分利用各组特征向量的互补作用,采取层次结构来获得系统的最佳性能。在车牌号图片库中测试其算法。实验表明,算法非常有效。     

Potassium ion release and enzyme secretion: adrenergic regulation by alpha- and beta-receptors

Epinephrine caused amylase secretion and K(+) release in rat parotid slices. Propranolol, which blocks beta-receptors, inhibited amylase secretion; phentolamine, which blocks alpha-receptors, inhibited K(+) release. Since enzyme secretion was associated with fusion of secretory granules to the cell membrane and K(+) release was associated with vacuole formation, it could be shown that both alpha- and beta-receptors are present in the same exocrine cell. The findings appear to exclude cyclic 3',5'-adenosine monophosphate as an intermediate in the alpha-receptor response.     

Production of immunoglobulin isotypes by Ly-1+ B cells in viable motheaten and normal mice

Almost all B cells in autoimmune mice with the viable motheaten (mev) mutation express the Ly-1 cell surface antigen, which marks a minor population of B cells constituting a separate lineage in normal mice. Immunoglobulins primarily of the M and G3 classes, which in both normal and mev mice contain high levels of lambda light chain, are produced in excess in mev mice. These and other observations suggest that the development of B cells that express Ly-1 is regulated independently from the development of B cells that do not express Ly-1. B cells bearing the Ly-1 surface antigen may play specialized roles in the normal immune system and in autoimmunity by regulating other B cells via lymphokines, by producing antibodies to self and certain foreign antigens, and by preferentially secreting immunoglobulin M and immunoglobulin G3.     

Gap junction development is correlated with insulin content in the pancreatic B cell

The development of gap junctions between insulin-containing B cells was quantitatively analyzed in islets of Langerhans isolated from rats treated with the sulfonylurea glibenclamid for 1, 2, or 7 days. Glibenclamid treatment was associated with a marked depletion of the insulin content of B cells and with an increase in the number and size of gap junctions between these cells. A significance correlation was found between these two events.