Increased apoptosis in lamina propria B cells during polymicrobial sepsis is FasL but not endotoxin mediated

2001 ◽  
Vol 280 (5) ◽  
pp. G812-G818 ◽  
Author(s):  
Chun-Shiang Chung ◽  
Weiyang Wang ◽  
Irshad H. Chaudry ◽  
Alfred Ayala

Recent studies from our laboratory demonstrated that mucosal lymphoid tissue such as Peyer's patch cells and lamina propria (LP) B lymphocytes from mice shows evidence of increased apoptosis after sepsis that is associated with localized inflammation/activation. The mechanism for this is poorly understood. Endotoxin as well as Fas/Fas ligand (FasL) have been shown to augment lymphocyte apoptosis; however, their contribution to the increase of apoptosis in LP B-cells during sepsis is not known. To study this, sepsis was induced by cecal ligation and puncture (CLP) in endotoxin-tolerant C3H/HeJ or FasL-deficient C3H/HeJ- FasLgld(FasL−) mice and LP lymphocytes were isolated 24 h later. Phenotypic, apoptotic, and functional indexes were assessed. The number of LP B cells decreased markedly in C3H/HeJ mice but not in FasL-deficient animals at 24 h after CLP. This was associated with comparable alteration in apoptosis and Fas antigen expression in the B cells of these mice. Septic LP lymphocytes also showed increased IgA production, which was absent in the FasL-deficient CLP mice. Furthermore, Fas ligand deficiency appeared to improve survival of septic challenge. These data suggest that the increase in B cell apoptosis in septic animals is partially due to a Fas/FasL-mediated process but not endotoxin.

Author(s):  
D.J. Unsworth

The gastrointestinal tract is protected by gut-associated lymphoid tissue that provides an environment where interaction occurs between luminal antigen and specially adapted immune tissue in Peyer’s patches (small intestine only) or lymphoid follicles. T and B lymphocytes primed in the gut migrate into the systemic circulation via the thoracic duct but home preferentially to the lamina propria of the intestine. Plasma cells of the lamina propria secrete immunoglobulin A as a dimer linked by a joining peptide....


2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Dimitra Vasileia Daikidou ◽  
MARIA STANGOU ◽  
Erasmia Sampani ◽  
Despoina Asouchidou ◽  
Vasiliki Nikolaidou ◽  
...  

Abstract Background and Aims Lymphocyte apoptosis, as a programmed mechanism of lymphocyte death, is essential in maintaining homeostasis and balance between inflammatory and immune reactions. Disturbances in the apoptotic progress, leading to fragmented lymphocytes, “late apoptotic” cells, may result in immunodeficiency, oncogenesis, atheromatosis, etc. Aim of the present study was to investigate the lymphocyte apoptotic progress in End Stage Renal Disease (ESRD) and the effect of dialysis. Method The study included patients on ESRD; measurements were performed at the first day of dialysis (T0) and repeated 6 months later (T6), while being on dialysis. Total lymphocytes and B lymphocytes (CD19+) were gated and stained with Annexin V to detect apoptotic cells; early and late apoptotic cells were quantified. The results were compared to age-matched healthy control group. Results ESRD patients had reduced lymphocyte and B cell count, 1550±592μ/L vs. 2692±690μ/L, p<0.001 and 120.4±80μ/L vs. 321.7±184.7μ/L, p=0.002, respectively, compared to controls. There was an increase in total lymphocytes and B cells, being on later apoptotic stages (LAS) in ESRD-T0 compared to controls, 0.3±0.8% vs. 0.06±0.1%, and 0.04±0.08% vs. 0.01±0.03%, respectively, although differences did not reach statistical significance. After 6 months on dialysis, a reduction was noticed in the population of lymphocytes on LAS, 0.18±0.2% from 0.34±0.8%, while there was an increase of B cells on LAS, 0.1±0.2% from 0.02±0.07, with subsequent alterations in total numbers of apoptotic cells were also evident Conclusion Late apoptotic changes affecting total and particularly B lymphocytes happen in ESRD, and initiation of dialysis seem to cause further alterations, which may be implicated in the increased morbidity and mortality of disease


2003 ◽  
Vol 40 (4) ◽  
pp. 395-404 ◽  
Author(s):  
J. Sarradell ◽  
M. Andrada ◽  
A. S. Ramírez ◽  
A. Fernández ◽  
J. C. Gómez-Villamandos ◽  
...  

Porcine enzootic pneumonia (PEN), caused by Mycoplasma hyopneumoniae (Mh), has been described in pigs in all geographic areas. The disease is characterized by high morbidity and low mortality rates in intensive swine production systems. A morphologic and immunohistochemical study was done to determine the cellular populations present in lung parenchyma of infected pigs, with special attention to the bronchus-associated lymphoid tissue (BALT). Polyclonal and monoclonal antibodies were used for the detection of antigens of Mh, T lymphocytes (CD3+, CD4+, and CD8+), IgG+ or IgA+ lymphocytes, and cells containing lysozyme, S-100 protein, major histocompatibility complex class II antigen or myeloid-histiocyte antigen. Findings in lung tissues associated with Mh infection were catarrhal bronchointerstitial pneumonia, with infiltration of inflammatory cells in the lamina propria of bronchi and bronchioles and alveolar septa. Hyperplasia of mononuclear cells in the BALT areas was the most significant histologic change. The BALT showed a high morphologic and cellular organization. Macrophages and B lymphocytes were the main cellular components of germinal centers. T lymphocytes were primarily located in perifollicular areas of the BALT, lamina propria and within the airway epithelium, and plasma cells containing IgG or IgA at the periphery of the BALT, in the lamina propria of bronchi and bronchioles, in alveolar septa, and around bronchial submucosal glands. The hyperplastic BALT in PEN cases consisted of macrophages, dendritic cells, T and B lymphocytes, and IgG+ and IgA+ plasma cells. CD4+ cells predominated over CD8+ cells. Local humoral immunity appears to play an important role in the infection.


Blood ◽  
1991 ◽  
Vol 78 (6) ◽  
pp. 1503-1515 ◽  
Author(s):  
G Inghirami ◽  
DR Foitl ◽  
A Sabichi ◽  
BY Zhu ◽  
DM Knowles

Abstract Monoclonal antibodies (MoAbs) specific for autoantibody associated cross-reactive idiotypes (CRIs) frequently recognize the Igs of neoplastic B cells in patients with chronic lymphocytic leukemia (CLL) and/or Waldenstrom's macroglobulinemia. Very little is known regarding the normal B cells expressing CRIs (CRI-positive B cells). Using a variety of MoAbs against CRIs we investigated the distribution and topographic localization of CRI-positive B cells in normal adult human lymphoid tissues. We found that CRI-positive B cells represent a significant B-cell subpopulation expressing surface IgM (greater than 90%), IgG (approximately 5%), or IgA (approximately 2%). CRI-positive B cells are homogeneously distributed throughout all lymphoid tissues, accounting for 10% to 15% of all B lymphocytes, with the exception of the thymus, in which they represent the predominant B cell population. Immunophenotypic studies showed (1) that a small subpopulation (3.7% +/- 0.8%) of CRI-positive B cells are activated in vivo, based on CD25 and CD38 antigen expression; and (2) that approximately 50% of CRI-positive B cells express the 67-Kd pan-T-lymphocyte CD5 antigen, suggesting that the CRI-positive B-cell subset and the recently described CD5-positive B-cell subset are closely related. This hypothesis is supported by the fact that CRI-positive B cells produce oligo or polyreactive Igs, which are a characteristic feature of CD5-positive B cells, and also by the fact that both B-cell subpopulations appear to use similar and restricted Ig VH gene family members.


Blood ◽  
1998 ◽  
Vol 91 (4) ◽  
pp. 1362-1372 ◽  
Author(s):  
Alfred Ayala ◽  
Ying Xin Xu ◽  
Carol A. Ayala ◽  
Diane E. Sonefeld ◽  
Shannon M. Karr ◽  
...  

Abstract Sepsis is reported to induce an increase in the rate of apoptosis (Ao), in immature lymphoid cells residing in hematopoietic tissues such as the thymus and bone marrow. Alternatively, secondary lymphoid tissue, such as the spleen exhibit little innate (unstimulated) Ao. However, it is unknown whether or not polymicrobial sepsis has any effects on the frequency of Aoin mucosal lymphoid tissue and what, if any, are the functional consequences of such a change. To assess this, Peyer's patch cells were harvested from C3H/HeN (endotoxin-sensitive) mice killed 12 or 24 hours after the onset of polymicrobial sepsis (cecal ligation and puncture [CLP]). The results indicate that the percentage of cells that were Ao+ as determined by flow cytometry were markedly increased at 24 hours, but not at 12 hours post-CLP. This correlates well with evidence of increased DNA fragmentation as well as histological changes observed both at a light and transmission electron microscopic level of the Peyer's patch Ao. Phenotypically, these changes were restricted to the B220+ (B-cell) population that also exhibited a marked increase of Fas/Apo-1 antigen expression. The functional consequence of this increased apoptosis appears to be associated with the endogenous stimulation (activation) of IgA production by mucosal B lymphocytes and increased nuclear c-Rel expression. Furthermore, we found that Peyer's patch lymphocytes isolated from C3H/HeJ-Faslgld(endotoxin-tolerant/Fas ligand- [FasL] deficient) as opposed to C3H/HeJ (endotoxin-tolerant) inbred mice did not exhibit increased Ao after CLP. These findings indicate that increased B-cell Ao appears to be a FasL-Fas antigen-mediated process, but is not due to endotoxin sensitivity. In conclusion, we speculate that the increased Fas-associated apoptosis detected in mucosal B cells (as opposed to splenic or bone marrow B cells) may be due to increased luminal antigens other than endotoxin, released due to gut barrier integrity breakdown during sepsis.


2000 ◽  
Vol 74 (1) ◽  
pp. 552-555 ◽  
Author(s):  
Jocelyn J. Jakubik ◽  
Mohammed Saifuddin ◽  
Daniel M. Takefman ◽  
Gregory T. Spear

ABSTRACT This study investigated the interaction of tonsil B lymphocytes with immune complexes containing human immunodeficiency virus (HIV IC) primary isolates and the infectivity of the B cell-bound HIV IC. Treatment of virus with a source of antibody and complement increased HIV IC binding to B cells by 5.6-fold. Most of the HIV IC that bound to B cells were not internalized but remained on the cell surface and were gradually released over 72 h. Cell-bound HIV IC were highly infectious for T cells while virus released by cultured B cells was only slightly infectious. Removal of HIV IC from the B-cell surface by protease treatment reduced the infection of T cells to near-background levels, indicating that infectious virus remained on the B-cell surface. These studies show that B lymphocytes can carry and transfer infectious HIV IC to T cells and thus suggest a novel mode of infection of T cells in lymphoid tissue that could be important for pathogenesis during HIV infection.


Blood ◽  
1987 ◽  
Vol 70 (6) ◽  
pp. 1750-1757 ◽  
Author(s):  
F Morabito ◽  
EF Prasthofer ◽  
NE Dunlap ◽  
CE Grossi ◽  
AB Tilden

Abstract We analyzed the expression of myelomonocytic-associated antigens on lymphocytes from B cell chronic lymphocytic leukemia (B-CLL) patients. Blood mononuclear cells were depleted of monocytes by one-step Percoll density gradient centrifugation and tested for antigen expression by fluorescent microscopy and flow cytometry. The reactivity of patient lymphocytes was as follows: 26 of 31 were positive for CD14 (Myr), 22 of 31 for a monocyte Fc receptor (MFC-1), 22 of 31 for CD11b (C3bi receptor), eight of 31 for CD15 (Leu-M1), five of 18 for CD13 (My 7), seven of 18 for My 9, and five of 30 for Mo 2. The B lymphocytes of B- CLL patients were also tested for the ability to produce interleukin 1 (IL-1) after depletion of monocytes and T lymphocytes. In 13 of 17 cases, B lymphocytes of patients produced IL-1 as detected in a mouse thymocyte proliferation assay and, in selected cases, a radioimmunoassay specific for IL-1 beta. The 13 cases that produced IL- 1 were also positive for the expression of one or more myelomonocytic- associated antigens, whereas the four cases that did not produce IL-1 lacked expression of these antigens. In conclusion, the malignant B cells of B-CLL patients frequently express a variety of antigens generally considered specific for myelomonocytic cells, and expression of these antigens is associated with the ability to produce IL-1.


Blood ◽  
1987 ◽  
Vol 70 (6) ◽  
pp. 1750-1757 ◽  
Author(s):  
F Morabito ◽  
EF Prasthofer ◽  
NE Dunlap ◽  
CE Grossi ◽  
AB Tilden

We analyzed the expression of myelomonocytic-associated antigens on lymphocytes from B cell chronic lymphocytic leukemia (B-CLL) patients. Blood mononuclear cells were depleted of monocytes by one-step Percoll density gradient centrifugation and tested for antigen expression by fluorescent microscopy and flow cytometry. The reactivity of patient lymphocytes was as follows: 26 of 31 were positive for CD14 (Myr), 22 of 31 for a monocyte Fc receptor (MFC-1), 22 of 31 for CD11b (C3bi receptor), eight of 31 for CD15 (Leu-M1), five of 18 for CD13 (My 7), seven of 18 for My 9, and five of 30 for Mo 2. The B lymphocytes of B- CLL patients were also tested for the ability to produce interleukin 1 (IL-1) after depletion of monocytes and T lymphocytes. In 13 of 17 cases, B lymphocytes of patients produced IL-1 as detected in a mouse thymocyte proliferation assay and, in selected cases, a radioimmunoassay specific for IL-1 beta. The 13 cases that produced IL- 1 were also positive for the expression of one or more myelomonocytic- associated antigens, whereas the four cases that did not produce IL-1 lacked expression of these antigens. In conclusion, the malignant B cells of B-CLL patients frequently express a variety of antigens generally considered specific for myelomonocytic cells, and expression of these antigens is associated with the ability to produce IL-1.


Blood ◽  
1991 ◽  
Vol 78 (6) ◽  
pp. 1503-1515
Author(s):  
G Inghirami ◽  
DR Foitl ◽  
A Sabichi ◽  
BY Zhu ◽  
DM Knowles

Monoclonal antibodies (MoAbs) specific for autoantibody associated cross-reactive idiotypes (CRIs) frequently recognize the Igs of neoplastic B cells in patients with chronic lymphocytic leukemia (CLL) and/or Waldenstrom's macroglobulinemia. Very little is known regarding the normal B cells expressing CRIs (CRI-positive B cells). Using a variety of MoAbs against CRIs we investigated the distribution and topographic localization of CRI-positive B cells in normal adult human lymphoid tissues. We found that CRI-positive B cells represent a significant B-cell subpopulation expressing surface IgM (greater than 90%), IgG (approximately 5%), or IgA (approximately 2%). CRI-positive B cells are homogeneously distributed throughout all lymphoid tissues, accounting for 10% to 15% of all B lymphocytes, with the exception of the thymus, in which they represent the predominant B cell population. Immunophenotypic studies showed (1) that a small subpopulation (3.7% +/- 0.8%) of CRI-positive B cells are activated in vivo, based on CD25 and CD38 antigen expression; and (2) that approximately 50% of CRI-positive B cells express the 67-Kd pan-T-lymphocyte CD5 antigen, suggesting that the CRI-positive B-cell subset and the recently described CD5-positive B-cell subset are closely related. This hypothesis is supported by the fact that CRI-positive B cells produce oligo or polyreactive Igs, which are a characteristic feature of CD5-positive B cells, and also by the fact that both B-cell subpopulations appear to use similar and restricted Ig VH gene family members.


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