Lymphocyte Subsets In Chronic Gvhd – a Key Role for B Cells?

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2311-2311
Author(s):  
Inken Hilgendorf ◽  
Brigitte Mueller-Hilke ◽  
Guenther Kundt ◽  
Ernst Holler ◽  
Petra Hoffmann ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Chronic Gvhd ◽  
Memory B Cells ◽  
Blood Samples ◽  
Cell Counts ◽  
Group 3 ◽  
Group 2 ◽  
B Cell Subsets ◽  
Group 1

Abstract Abstract 2311 Background: Chronic graft-versus host disease (cGVHD) features certain similarities with autoimmune diseases. The pathogenesis of cGVHD after allogeneic hematopoietic stem cell transplantation (alloHSCT), however, is poorly understood. Methods: Peripheral blood samples from 52 pts with active (median day 976, range 177–2773) (group 1), 28 pts with resolved (median day 1207, range 147–2849) (group 2) and 18 pts without cGVHD (median day 1015, range 124–2655) (group 3) were analysed for T and B cell subsets by FACS. 47 pts were transplanted from matched related donors, 40 pts from matched and 11 from mismatched unrelated donors. In addition, blood samples from 20 patients with and 10 patients without history of cGVHD were tested for: antinuclear antibody (ANA), anti-neutrophil cytoplasmatic antibody (ANCA), antimitochondrial antibody (AMA), anti-smooth-muscle antibody (ASMA) and double stranded DNA (dsDNA). Chronic GVHD was evaluated using criteria and guidelines of the National Institute of Health (mild n=16, moderate=18, severe n=18). Results: The absolute CD19+ B cell counts (median in 109/l) in pts with active chronic GVHD (0.03; range 0–2.59) were subnormal and lower than in pts of group 2 (0.140; range 0.001–0.856; p 0.019) and group 3 (0.175; range 0.20–0.553; p 0.002). Significant differences in absolute numbers of the CD27− B cell compartment, including immature (CD19+ CD27− CD38++CD20+IgM+) and transitional B cells (CD19+ CD27− CD38++CD10+CD20+IgM+), (median in 109/l: group1: 0.015; range 0–0.499 vs. group 2: 0.090; range 0–0.667 or vs. group 3: 0.158; range 0.02–0.52; both p<0.001) as well as class switched memory B cells (median in 106/l: 0.045; range 0–96.00 vs. 3.40; range 0–69.35; p 0.032 or vs. 7.40; range 0–56.83; p 0.003) were observed between the groups. Of interest, the CD 27+IgD+IgM+ B cell subpopulation (median in 106/l) is lacking in pts with active cGVHD (0; range 0–1.35) in contrast to patients with resolved (0.43, range 0–17.47; p<0.001) or pts who never experienced cGVHD (1.69; range 0–10.00; p<0.001). The counts of CD8+ T cells (median in 109/l) were significantly lower in pts of group 1 (0.257, range 0.01–1.76) compared to pts of group 2 (0.373; range 0 –1.96; p 0.010) or group 3 (0.545; range 0.06–1.61; p 0.027). No significant differences in CD4+ T cell counts (median in 109/l: 0.274 vs. 0.355 vs. 0.293) including naïve and memory CD4+ T cells as well as regulatory CD25+CD4+ FoxP3+ T cell counts (median in 106/l: 8.11 vs. 6.55 vs. 9.72) were observed between the three groups. In patients with cGVHD ANA was positive in 35% (7/20), ASMA in 20% (4/20) and AMA in 5% (1/20). ANA was positive in 36% (4/11) and ASMA in 27% (3/11) of patients without cGVHD. AMA and dsDNA were negative in all patients without cGVHD and ANCA was negative in all tested patients. 10% (3/31) of patients showed more than one autoantibody. Conclusion: Our data confirm a close association of diminished B cell counts with cGVHD while no difference of the tested autoantibodies was observed between pts with and without cGVHD. The lack of CD 27+IgD+IgM+ B cells in pts with cGVHD indicates functional asplenia in these pts, because IgM+ memory B cells are dependent upon a functional spleen for their generation and/or survival. Analysis of B cell subsets can provide a diagnostic tool for monitoring cGVHD activity but requires prospective evaluation. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Variation of B cell subsets with age in healthy Malawians

PLoS ONE ◽  
2021 ◽  
Vol 16 (7) ◽  
pp. e0254320
Author(s):  
Wilson L. Mandala ◽  
Herbert Longwe
Keyword(s):  
B Cells ◽  
B Cell ◽  
Lymphocyte Subsets ◽  
Venous Blood ◽  
Memory B Cells ◽  
Age Group ◽  
Blood Samples ◽  
Opposite Trend ◽  
Different Ages ◽  
B Cell Subsets

Although a number of previous studies have shown that different lymphocyte subsets, including B cells, vary with age, how different B cell subsets vary with age in Malawian population has not been shown before. We recruited Malawian participants of different ages and analyzed their venous blood samples for different B cell subsets. We found that both percentage and absolute counts of B cells varied with age peaking in the 7 to 12 months age group. Proportion of naïve B cells was highest in neonates and decreased with age whereas the percentage of memory B cells was lowest in neonates and increased with age. When we zeroed in on the age band within which the proportion of B cells was highest, both classical and activated memory B cells increased with age and the naïve followed the opposite trend. These results provide additional knowledge in our understanding of the dynamics of B cell subsets in individuals of a specific ethnicity as they age.

Cholinesterase Activities and Oxidative Stress in Cattle Experimentally Exposed to Nitrate/Nitrite in Cultivated Pasture with Different Fertilization Schemes

2018 ◽  
Vol 46 (1) ◽  
Author(s):  
Ricardo Christ ◽  
Aleksandro Schafer Da Silva ◽  
Mateus Eloir Grabriel ◽  
Luan Cleber Henker ◽  
Renan Augusto Cechin ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Enzyme Activity ◽  
Cholinesterase Activity ◽  
Blood Samples ◽  
Group 3 ◽  
Cholinesterase Activities ◽  
Group 2 ◽  
Nitrate And Nitrite ◽  
And Oxidative Stress ◽  
Group 1

  Background: Nitrate and nitrite poisoning is associated with pasture intake that has high nitrate levels and leads to acute methemoglobinemia. Pasture may accumulate nitrate under certain conditions, such as excessively fertilized soil or en­vironmental conditions that enhance the N absorption (rain preceded by a period of drought). After ingestion of plants, this substrate reaches the rumen and, in physiological conditions, is reduced to nitrite and afterward to ammonia. The aim of this study was to evaluate changes in cholinesterase activities and oxidative stress caused by subclinical poisoning for nitrate and nitrite in cattle fed with Pennisetum glaucum in three different fertilization schemes. Materials, Methods & Results: In order to perform the experimental poisoning, the pasture was cultivated in three dif­ferent paddocks: with nitrogen topdressing (urea; group 1), organic fertilizer (group 2) or without fertilizer (group 3; control). Nitrate accumulation in forage was evaluated by the diphenylamine test. After food fasting of 12 h, nine bovine were randomly allocated to one of the experimental groups and fed with fresh forage (ad libitum) from respective pad­dock. In different time points from beginning of pasture intake (0, 2, 4, 6 and 9 h) heart rate and respiratory frequency were assessed, as well as mucous membrane color and behavioral changes. Blood samples from jugular vein into vials with and without anticoagulant were collected. From blood samples, serum nitrite levels, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzyme activity were evaluated, as well as oxidative stress through the following param­eters: levels of nitrate/nitrite (NOx), thiobarbituric acid reactive substances (TBARS) and reactive oxygen species (ROS), beyond the antioxidant system by enzyme activity measurement of catalase (CAT) and superoxide dismutase (SOD). The diphenylamine test was positive to group 1 and 2, so that the pasture presented 3.16 mg/kg, 2.98 mg/kg and 1.67 mg/kg of nitrate for group 1, 2 and 3, respectively. In addition, cows from group 1 demonstrated increased (P < 0.05) nitrite levels in serum, compared to other groups, and greater heart rate after 9 h (P < 0.05). The AChE and BChE activity in group 1 showed significant increase (P < 0.05) at 4 and 6 h (AChE), and 4 and 9 h (BChE) compared to group 3. Also, NOx levels were lower at 6 and 9 h (P < 0.05) and at 9 h (P < 0.05) for animals of group 1 and 2, respectively, when compared to group 3. Furthermore, in the group 1 levels of ROS and TBARS were significantly higher (P < 0.05) after 2 and 4 h, and 6 and 9 h compared to other groups, respectively. The CAT activity increased significantly (P < 0.05) with 2 and 4 h of the experiment, but on the other hand, decreased at 6 and 9 h in group 1. Nevertheless, the animals from group 2 presented only a significant reduction in this enzyme activity at 9 h. Furthermore, SOD activity was reduced in animals of groups 1 (P < 0.05) at 4, 6 and 9 h, compared to other groups. Discussion: It was concluded that the nitrate and nitrite poisoning by pasture intake cultivated and fertilized with urea leads to increased levels of serum nitrite, as well as the cholinesterase activity and causes oxidative stress in cattle. It is conjectured that the cholinesterase activity and oxidative stress may assist in understanding the pathophysiology of changes caused by poisoning.Keywords: plant toxicology, poisoning, methemoglobin, cholinergic system, oxidative stress.

scholarly journals Cell Loss from the Nucleus Basalis of Meynert in Alzheimer's Disease

1986 ◽  
Vol 13 (S4) ◽  
pp. 435-440 ◽  
Author(s):  
R. Doucette ◽  
M. Fisman ◽  
V.C. Hachinski ◽  
H. Mersky
Keyword(s):  
Paraffin Section ◽  
Neuronal Loss ◽  
Cell Loss ◽  
Nucleus Basalis ◽  
Nucleus Basalis Of Meynert ◽  
Cell Counts ◽  
Group 3 ◽  
Group 2 ◽  
Death Group ◽  
Group 1

Abstract:We examined the degree of neuronal loss from the nucleus basalis of Meynert (nbM) in two groups of Alzheimer patients differing in the degree of intellectual impairment. Significant cell loss from the nbM was found only in the more severely demented group of patients. Mean cell counts (per lOu, paraffin section) were compiled separately for the anterior, intermediate and posterior subdivisions of the human nbM in three groups of subjects: Group 1 (N = 4) was severely demented and was untestable on the Extended Scale for Dementia (ESD) for at least the last two years of life; Group 2 (N = 4) was less demented and had completed at least one ESD test within 12 months of death; Group 3 (five controls) had died of non-neurological causes. In Group 2 there was a small (but insignificant) trend toward cell loss in the anterior subdivision, and a normal complement of neurons in both the intermediate and posterior subdivisions. There was, however, significant cell loss from all subdivisions of Group 1. How these cell counts may relate to the severity of the dementia is discussed.

scholarly journals Leucocytes and Th-associated cytokine profile of HIV-leishmaniasis coinfected patients attending the Abuja Teaching Hospital, Nigeria

2020 ◽  
Vol 89 (1) ◽  
pp. e408
Author(s):  
Idris Nasir Abdullahi ◽  
Anthony Uchenna Emeribe ◽  
Hafeez Aderinsayo Adekola ◽  
Habiba Yahaya Muhammad ◽  
Abdurrahman El-fulaty Ahmad ◽  
...  
Keyword(s):  
Teaching Hospital ◽  
Leishmania Donovani ◽  
Cell Counts ◽  
Tnf Α ◽  
Group 3 ◽  
Group 2 ◽  
Cell Subpopulations ◽  
Healthy Persons ◽  
Group 1 ◽  
Apparently Healthy

Introduction. T helper cells (Th)-1 and -2 cytokines homeostasis control or predict clinical outcome of infected persons, especially those with HIV/AIDS. This case-control study evaluated the leucocyte differentials, TNF-α, IL-2 and -10 levels, among HIV-infected persons with serological evidence of leishmaniasis attending the University of Abuja Teaching Hospital, Nigeria. Material and Methods. This study involved blood samples from 28 HIV-infectedwith Leishmania donovani rK39 and IgG positive (group 1), 30 age- and sex-matched HIV-infected individuals without Leishmania antibodies (group 2) and 30 apparently healthy persons without HIV and Leishmania antibodies (group 3). Full blood counts, TNF-α, IL-2 and IL-10 levels were analysed using an automated haematology analyser and ELISA, respectively. Structured questionnaires were used to collate biochemical and clinical data from participants. Results. Ten (35.7%) participants in group 1 were on ART, 15 (50%) in group 2 were on ART, while group 3 were ART naïve. There were significantly higher values in basophil (4.4 ± 2.5%) and eosinophil counts (12.9 ± 3.8%) in HIV/Leishmania coinfected persons (p˂0.005), whereas other white cell subpopulations were significantly lower in the HIV/Leishmania coinfected participants (p˂0.05). There were significantly reduced CD4+ T cell counts (119 ± 26 vs 348 ± 63 vs 605 ± 116 cells/mm3), TNF-α (36.82 ± 8.21 vs 64.67 ± 12.54 vs 254.98 ± 65.59 pg/mL) and IL-2 levels (142.14 ± 20.91 vs 507.6 ± 84.42 vs 486.62 ± 167.87 pg/mL) among HIV/Leishmania coinfected participants compared to group 2 and group 3 participants, respectively. However, higher IL-10 levels (80.35 ± 14.57 pg/mL) were detected in HIV/Leishmania coinfected participants compared to the HIV mono-infected (62.2 ± 10.43 pg/mL) and apparently healthy persons (23.97 ± 4.88 pg/mL; p˂0.001). Conclusion. Eosinophil and basophil counts, and serum IL-10 level were high in HIV/Leishmania coinfected patients demonstrating parasite-induced hypersensitivity and immunosuppression.

scholarly journals Memory B Cells that Cross-React with Group 1 and Group 2 Influenza A Viruses Are Abundant in Adult Human Repertoires

Immunity ◽  
2018 ◽  
Vol 48 (1) ◽  
pp. 174-184.e9 ◽  
Author(s):  
Kevin R. McCarthy ◽  
Akiko Watanabe ◽  
Masayuki Kuraoka ◽  
Khoi T. Do ◽  
Charles E. McGee ◽  
...  
Keyword(s):  
B Cells ◽  
Influenza A ◽  
Memory B Cells ◽  
Influenza A Viruses ◽  
Adult Human ◽  
Group 2 ◽  
Group 1

Abstract 196: The Characteristics of Patients with Kawasaki disease Presented with Fever and Cervical Lymphadenopathy at Admission

Circulation ◽  
2015 ◽  
Vol 131 (suppl_2) ◽  
Author(s):  
yeo hyang kim ◽  
Chae Ok Shin ◽  
Myung Chul Hyun ◽  
Dong Seok Lee
Keyword(s):  
Intravenous Immunoglobulin ◽  
Cervical Lymphadenopathy ◽  
Systemic Steroid ◽  
Line Treatment ◽  
Cell Counts ◽  
Blood Cell Counts ◽  
Group 3 ◽  
Group 2 ◽  
White Blood Cell Counts ◽  
Group 1

Purpose: Of the principal diagnostic criteria of Kawasaki disease (KD), cervical lymphadenopathy is the least common. However, it may be misdiagnosed as bacterial cervical lymphadenitis. We evaluated the characteristics of patients with KD presenting with only fever and cervical lymphadenopathy at admission. Methods: This study enrolled patients diagnosed KD from January 2013 to May 2014. All of patients were divided to three groups: group 1 had only fever and cervical lymphadenopathy at admission; group 2 had typical manifestations with cervical lymphadenopathy; group 3 had typical manifestations without cervical lymphadenopathy. Results: Ninety eight patients (group 1 in 13, group 2 in 31, group 3 in 54) were examined. The median age of group 1 was significantly older than group 2 and 3 ( P =0.001). The duration of fever before admission at our hospital was more prolonged in group 1 than in group 2 and 3 ( P =0.001). In comparison between groups, the laboratory results at the admission day were not significantly different. However, group 1 showed significantly elevated white blood cell counts, elevated neutrophil counts, and decreased lymphocyte counts after first intravenous immunoglobulin administration ( P =0.001, P =0.001, and P =0.003). The frequency of additional intravenous immunoglobulin treatment did not have significant difference. Group 1 had significantly increased duration of hospitalization, and frequency of second line treatment such as systemic steroid or infliximab than group 2 and 3 ( P =0.000, P =0.024, and P =0.007). The development of a coronary artery dilatation (z score >2.5) was higher in group 1 than in group 3 ( P =0.008). Conclusions: KD with cervical lymphadenopathy as main presentation indicates a severe form of KD associated with increased risks of second line treatment such as systemic steroid or infliximab and coronary artery dilatation. KD should be suspected in the older children with antibiotics non-responsive, prolonged fever and cervical lymphadenopathy. For differentiation between responder and non-responder for first line treatment, white blood cell counts and their subset after first intravenous immunoglobulin administration may be beneficial.

scholarly journals Complexity of the human memory B-cell compartment is determined by the versatility of clonal diversification in germinal centers

2015 ◽  
Vol 112 (38) ◽  
pp. E5281-E5289 ◽  
Author(s):  
Bettina Budeus ◽  
Stefanie Schweigle de Reynoso ◽  
Martina Przekopowitz ◽  
Daniel Hoffmann ◽  
Marc Seifert ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Cell Clone ◽  
Human Memory ◽  
Memory B Cells ◽  
Sequencing Analysis ◽  
Cell Compartment ◽  
Memory B Cell ◽  
Cell Clones ◽  
B Cell Subsets

Our knowledge about the clonal composition and intraclonal diversity of the human memory B-cell compartment and the relationship between memory B-cell subsets is still limited, although these are central issues for our understanding of adaptive immunity. We performed a deep sequencing analysis of rearranged immunoglobulin (Ig) heavy chain genes from biological replicates, covering more than 100,000 memory B lymphocytes from two healthy adults. We reveal a highly similar B-cell receptor repertoire among the four main human IgM+ and IgG+ memory B-cell subsets. Strikingly, in both donors, 45% of sequences could be assigned to expanded clones, demonstrating that the human memory B-cell compartment is characterized by many, often very large, B-cell clones. Twenty percent of the clones consisted of class switched and IgM+(IgD+) members, a feature that correlated significantly with clone size. Hence, we provide strong evidence that the vast majority of Ig mutated B cells—including IgM+IgD+CD27+ B cells—are post-germinal center (GC) memory B cells. Clone members showed high intraclonal sequence diversity and high intraclonal versatility in Ig class and IgG subclass composition, with particular patterns of memory B-cell clone generation in GC reactions. In conclusion, GC produce amazingly large, complex, and diverse memory B-cell clones, equipping the human immune system with a versatile and highly diverse compartment of IgM+(IgD+) and class-switched memory B cells.

scholarly journals In VitroMeasles Virus Infection of Human Lymphocyte Subsets Demonstrates High Susceptibility and Permissiveness of both Naive and Memory B Cells

2018 ◽  
Vol 92 (8) ◽  
pp. e00131-18 ◽  
Author(s):  
Brigitta M. Laksono ◽  
Christina Grosserichter-Wagener ◽  
Rory D. de Vries ◽  
Simone A. G. Langeveld ◽  
Maarten D. Brem ◽  
...  
Keyword(s):  
T Cells ◽  
B Cells ◽  
B Cell ◽  
Immune Suppression ◽  
Peripheral Blood ◽  
Measles Virus ◽  
Memory B Cells ◽  
T And B Cells ◽  
B Cell Subsets

ABSTRACTMeasles is characterized by a transient immune suppression, leading to an increased risk of opportunistic infections. Measles virus (MV) infection of immune cells is mediated by the cellular receptor CD150, expressed by subsets of lymphocytes, dendritic cells, macrophages, and thymocytes. Previous studies showed that human and nonhuman primate memory T cells express higher levels of CD150 than naive cells and are more susceptible to MV infection. However, limited information is available about the CD150 expression and relative susceptibility to MV infection of B-cell subsets. In this study, we assessed the susceptibility and permissiveness of naive and memory T- and B-cell subsets from human peripheral blood or tonsils toin vitroMV infection. Our study demonstrates that naive and memory B cells express CD150, but at lower frequencies than memory T cells. Nevertheless, both naive and memory B cells proved to be highly permissive to MV infection. Furthermore, we assessed the susceptibility and permissiveness of various functionally distinct T and B cells, such as helper T (TH) cell subsets and IgG- and IgA-positive memory B cells, in peripheral blood and tonsils. We demonstrated that TH1TH17 cells and plasma and germinal center B cells were the subsets most susceptible and permissive to MV infection. Our study suggests that both naive and memory B cells, along with several other antigen-experienced lymphocytes, are important target cells of MV infection. Depletion of these cells potentially contributes to the pathogenesis of measles immune suppression.IMPORTANCEMeasles is associated with immune suppression and is often complicated by bacterial pneumonia, otitis media, or gastroenteritis. Measles virus infects antigen-presenting cells and T and B cells, and depletion of these cells may contribute to lymphopenia and immune suppression. Measles has been associated with follicular exhaustion in lymphoid tissues in humans and nonhuman primates, emphasizing the importance of MV infection of B cellsin vivo. However, information on the relative susceptibility of B-cell subsets is scarce. Here, we compared the susceptibility and permissiveness toin vitroMV infection of human naive and memory T- and B-cell subsets isolated from peripheral blood or tonsils. Our results demonstrate that both naive and memory B cells are more permissive to MV infection than T cells. The highest infection levels were detected in plasma cells and germinal center B cells, suggesting that infection and depletion of these populations contribute to reduced host resistance.

scholarly journals Paraneoplastic hematological, biochemical, and hemostatic abnormalities in female dogs with mammary neoplasms

2017 ◽  
Vol 37 (5) ◽  
pp. 479-484 ◽  
Author(s):  
Naila C.B. Duda ◽  
Stella de F. Valle ◽  
Juliana P. Matheus ◽  
Natália C. Angeli ◽  
Luciane C. Vieira ◽  
...  
Keyword(s):  
Mammary Cancer ◽  
Tumor Staging ◽  
Tumor Type ◽  
Thrombin Time ◽  
Coagulation Test ◽  
Laboratory Findings ◽  
Blood Samples ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

ABSTRACT: Paraneoplastic laboratory abnormalities are identified in several types of cancers in dogs and cats. In veterinary medicine, particularly in mammary cancer, there are few studies that correlate abnormal laboratory findings with tumor type and staging. The aim of this study was to evaluate hematological, biochemical, and hemostatic abnormalities and correlate them with mammary tumor staging in female dogs with mammary cancer. Blood samples from 24 female dogs were evaluated, and the hematological, biochemical, and hemostatic parameters were correlated with tumor staging obtained by physical examination, imaging exams, and histopathological surgical biopsies. The groups were organized according to tumor staging: group 1 (stages I and II), group 2 (stage III), and group 3 (stages IV and V). Anemia, neutrophilic leukocytosis, monocytosis, eosinophilia, thrombocytosis, hypoalbuminemia, hypocalcemia, hypoglycemia, and low blood urea were observed. The variables MCHC, TPP, and RDW were correlated with tumor staging with no clinical relevance. Thrombin time and fibrinogen were significant between the groups in the coagulation test, being associated with tumor staging. The findings suggest influence of the proinflammatory cytokines released during tumor growth.

A role for Toll-like receptors in acquired immunity: up-regulation of TLR9 by BCR triggering in naive B cells and constitutive expression in memory B cells

Blood ◽  
2003 ◽  
Vol 101 (11) ◽  
pp. 4500-4504 ◽  
Author(s):  
Nadia L. Bernasconi ◽  
Nobuyuki Onai ◽  
Antonio Lanzavecchia
Keyword(s):  
B Cells ◽  
B Cell ◽  
Constitutive Expression ◽  
Human Memory ◽  
Cell Receptor ◽  
Primary Response ◽  
Memory B Cells ◽  
Toll Like Receptors ◽  
Polyclonal Activation ◽  
B Cell Subsets

Abstract Toll-like receptors (TLRs) are pattern recognition receptors that trigger innate immunity. In this study we investigated the expression of 10 TLRs in human naive and memory B-cell subsets. We report that in human naive B cells most TLRs are expressed at low to undetectable levels, but the expression of TLR9 and TLR10 is rapidly induced following B-cell-receptor (BCR) triggering. In contrast, memory B cells express several TLRs at constitutively high levels. The differential expression of TLR9 correlates with responsiveness to its agonist, CpG DNA. Thus, human memory B cells proliferate and differentiate to immunoglobulin (Ig)–secreting cells in response to CpG, while naive B do so only if simultaneously triggered through the BCR. The BCR-induced expression of TLRs in human naive B cells prevents polyclonal activation in a primary response, because it restricts stimulation to antigen-specific B cells. In contrast, the constitutive expression of TLRs in memory B cells allows polyclonal activation of the entire memory pool. Thus, in human B cells TLRs are downstream of BCR and play a role both in the primary response and in the memory phase.

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