scholarly journals BAFF Inhibition Effectively Suppresses the Development of Anti-HLA.A2 Antibody in the Highly Sensitized Mouse Model

2021 ◽  
Vol 22 (2) ◽  
pp. 861
Author(s):  
Ji Won Min ◽  
Yoo-Jin Shin ◽  
Hyeyoung Lee ◽  
Bo-Mi Kim ◽  
Ki Hyun Park ◽  
...  
Keyword(s):  
B Cells ◽  
Mouse Model ◽  
B Cell ◽  
Control Group ◽  
B Cell Differentiation ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Skin Allografts ◽  
Significant Difference ◽  
Desensitization Therapy

B cell activating factor (BAFF) is a cytokine that plays a role in the survival, proliferation and differentiation of B cells. We proposed to observe the effects of BAFF inhibition on the humoral immune responses of an allosensitized mouse model using HLA.A2 transgenic mice. Wild-type C57BL/6 mice were sensitized with skin allografts from C57BL/6-Tg (HLA-A2.1)1Enge/J mice and were treated with anti-BAFF monoclonal antibody (mAb) (named Sandy-2) or control IgG1 antibody. HLA.A2-specific IgG was reduced in BAFF-inhibited mice compared to the control group (Δ-13.62 vs. Δ27.07, p < 0.05). BAFF inhibition also resulted in increased pre-pro and immature B cell proportions and decreased mature B cells in the bone marrow (p < 0.05 vs. control). In the spleen, an increase in transitional B cells was observed with a significant decrease in marginal and follicular B cells (p < 0.05 vs. control). There was no significant difference in the proportions of long-lived plasma and memory B cells. Microarray analysis showed that 19 gene probes were significantly up- (>2-fold, p < 0.05) or down-regulated (≤2-fold, p < 0.05) in the BAFF-inhibited group. BAFF inhibition successfully reduced alloimmune responses through the reduction in alloantibody production and suppression of B cell differentiation and maturation. Our data suggest that BAFF suppression may serve as a useful target in desensitization therapy.

scholarly journals Essential Immunoregulatory Role for BCAP in B Cell Development and Function

2002 ◽  
Vol 195 (5) ◽  
pp. 535-545 ◽  
Author(s):  
Tetsuo Yamazaki ◽  
Kiyoshi Takeda ◽  
Kumiko Gotoh ◽  
Hiroshi Takeshima ◽  
Shizuo Akira ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Cell Receptor ◽  
Cell Development ◽  
B Cell Development ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Phosphoinositide 3 Kinase ◽  
And Function ◽  
B Cell Deficiency

BCAP was recently cloned as a binding molecule to phosphoinositide 3-kinase (PI3K). To investigate the role of BCAP, mutant mice deficient in BCAP were generated. While BCAP-deficient mice are viable, they have decreased numbers of mature B cells and B1 B cell deficiency. The mice produce lower titers of serum immunoglobulin (Ig)M and IgG3, and mount attenuated responses to T cell–independent type II antigen. Upon B cell receptor cross-linking, BCAP-deficient B cells exhibit reduced Ca2+ mobilization and poor proliferative responses. These findings demonstrate that BCAP plays a pivotal immunoregulatory role in B cell development and humoral immune responses.

Dok-3 plays a nonredundant role in negative regulation of B-cell activation

Blood ◽  
2007 ◽  
Vol 110 (1) ◽  
pp. 259-266 ◽  
Author(s):  
Chee-Hoe Ng ◽  
Shengli Xu ◽  
Kong-Peng Lam
Keyword(s):  
B Cells ◽  
B Cell ◽  
Cell Activation ◽  
Cell Receptor ◽  
Negative Regulation ◽  
Myelogenous Leukemia ◽  
Type I ◽  
B Cell Activation ◽  
Humoral Immune ◽  
Humoral Immune Responses

p62dok and Dok-3 are members of the Dok family of adaptors found in B cells, with the former cloned as a substrate of the p210bcr/abl oncoprotein in Ph + chronic myelogenous leukemia. A role for p62dok in FcγRIIB–mediated negative regulation of B-cell proliferation had been established previously. Here, we generated Dok-3−/− mice to assess the function of Dok-3 in B cells. Mice lacking Dok-3 have normal B-cell development but possess higher level of IgM antibodies in their sera. In comparison to wild-type mice, Dok-3−/− mice mounted significantly enhanced humoral immune responses to T cell–independent type I and II antigens. Dok-3–deficient B cells hyperproliferated, exhibited elevated level of calcium signaling as well as enhanced activation of NF-κB, JNK, and p38MAPK in response to B-cell receptor (BCR) engagement. In the absence of Dok-3, the localization of the inhibitory phosphatase SHIP-1 to the plasma membrane is intact while its phosphorylation is compromised, suggesting that Dok-3 could function to facilitate or sustain the activation of SHIP-1. The phenotype and responses of Dok-3−/− mice and B cells could be differentiated from those of the Dok-1−/− counterparts. Hence, we propose that Dok-3 plays a distinct and nonredundant role in the negative regulation of BCR signaling.

MO008B LYMPHOCYTE SUBSET CHANGES IN PRIMARY MEMBRANEOUS NEPHROPATHY

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Nooshin Dalili ◽  
Fatemeh Pour-Reza Gholi ◽  
Katayoun Hasanzadeh ◽  
Sara Assadiasl
Keyword(s):  
B Cells ◽  
B Cell ◽  
B Lymphocytes ◽  
Standard Treatment ◽  
Control Group ◽  
P Value ◽  
Healthy Controls ◽  
Memory B Cell ◽  
Wide Range ◽  
Significant Difference

Abstract Background and Aims Primary membranous nephropathy (PMN) is the most common cause of nephrotic syndrome (NS) in adults. Rituximab a chimeric monoclonal anti-CD20 antibody has been supposed to eliminate autoantibody-producing B cells via direct signaling, complement-mediated cytotoxicity (CMC), and antibody-dependent cellular cytotoxicity (ADCC). According to the fact that a wide range of B lymphocytes may carry this marker, we aimed to identify which subset is more (or less) frequent in PMN patients and which one is more affected by rituximab administration. Method Three groups were enrolled in the present study. They included a healthy control group and two patient groups having the clinical, laboratory, and pathological diagnostic criteria of PMN, comprising either patients on standard treatment or patients on standard treatment plus rituximab. The latter group was studied just before receiving rituximab (pre-rituximab) and two months later (post rituximab). Peripheral blood mononuclear cells (PBMCs) were isolated using Ficoll-hypaque (inno-train, Germany) gradient. Afterward, cells were adjusted to a concentration of 1 _ 106 cells/mL and stained with mouse antihuman CD19-Cy5-conjugated antibody (Cytognos, Spain), mouse antihuman CD24-PE-conjugated antibody (Cytognos, Spain), and mouse antihuman CD38-FITC-conjugated antibody (Cytognos, Spain). Flow cytometry performed by FACS Calibur (BDFacs Calibur Becton Dickinson, USA). Results The total lymphocyte percentage was higher in PMN patients receiving either standard treatment or rituximab than in healthy controls (standard-treatment vs. control: P value = 0.001, pre-rituximab vs. control: P value =0.001). In post-rituximab analysis, CD19+ cell count showed notable reduction (P value = 0.003) B CD19+CD24+CD38- cells, representing the memory B cell population, did not show any significant difference between healthy controls and patients. Furthermore, the count of these cells did not decrease significantly two months after rituximab administration. The subset of CD19+CD24-CD38+ B lymphocytes, a class of naïve/mature lymphocytes with normal function, was significantly higher in the control group than in standard treatment patients (P value = 0.01). However, no statistically significant difference was found in CD19+CD24-CD38+B lymphocytes neither between the rituximab and control groups nor between pre-rituximab and post-rituximab patients. Conclusion The number of regulatory B cells decreased in both standard treatment and rituximab-receiving PMN patients and the proportion of naïve/mature B-lymphocytes was lower in the former group. Moreover, the memory B cells count did not reduce significantly two months after rituximab administration. Hence, it might be the best choice to target the memory B cell subset in immunosuppressive therapy while avoiding the Breg or naïve/mature B lymphocyte depletion to obtain more favorable sustained outcomes.

scholarly journals The collaborative phenotype of secondary B cells is determined by T lymphocytes during in vivo immunization.

1982 ◽  
Vol 155 (2) ◽  
pp. 574-586 ◽  
Author(s):  
N A Speck ◽  
S K Pierce
Keyword(s):  
T Cells ◽  
B Cells ◽  
B Cell ◽  
Cell Populations ◽  
Antibody Synthesis ◽  
Humoral Immune ◽  
Igg1 Antibody ◽  
Humoral Immune Responses

Previous studies have demonstrated that the B cells in immune and nonimmune mice manifest different major histocompatibility complex (MHC) collaborative phenotypes with antigen-specific T cells. Immune, or secondary B cells require syngeneic-like MHC recognition by collaborating T cells, and in its absence fail to be stimulated. Primary B cells manifest a much less stringent requisite for MHC recognition by T cells, and under conditions in which secondary B cells fail to be stimulated, primary B cells are stimulated to secrete IgM antibody. Experiments were conducted to determine whether the acquisition of the secondary B cells' MHC collaborative phenotype was dependent on the presence of T cells during in vivo immunization. B cell populations from T dependently and T independently immunized conventional BALB/c and athymic BALB/c nu/nu mice were compared in their ability to collaborate with allogeneic T cells. Although antigen alone promotes the differentiation of several secondary B cell characteristics, including an increase in the frequency of antigen-specific B cells and a preference for IgG1 antibody synthesis in vitro, the acquisition of the secondary B cells' MHC collaborative phenotype was dependent on the presence of T cells during in vivo immunization. B cell populations from T dependently and T independently immunized conventional BALB/c and athymic BALB/c nu/nu mice were compared in their ability to collaborate with allogeneic T cells. Although antigen alone promotes the differentiation of several secondary B cell characteristics, including an increase in the frequency of antigen-specific B cells and a preference of IgG1 antibody synthesis in vitro, the acquisition of the secondary B cells' MHC collaborative phenotype was found to be dependent on the presence of T cells during in vivo immunization. Thus, the restriction imposed on T cell-B-cell-collaborative interactions in secondary humoral immune responses appears to be the result of T dependent antigen-driven events.

Naive recirculating B cells mature simultaneously in the spleen and bone marrow

Blood ◽  
2006 ◽  
Vol 109 (6) ◽  
pp. 2339-2345 ◽  
Author(s):  
Annaiah Cariappa ◽  
Catharine Chase ◽  
Haoyuan Liu ◽  
Paul Russell ◽  
Shiv Pillai
Keyword(s):  
Bone Marrow ◽  
B Cells ◽  
B Cell ◽  
Single Pulse ◽  
Lymphoid Organs ◽  
Cell Maturation ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
B Cell Maturation ◽  
Secondary Lymphoid Organs

Abstract We have recently demonstrated that IgDhi B cells can occupy an extravascular perisinusoidal niche in the bone marrow in addition to the well-established follicular niche in conventional secondary lymphoid organs. The spleen has long been considered to be the site at which newly formed B lymphocytes mature into IgDhi naive recirculating B cells, but the existence of mutant mice that have selectively lost mature B cells in the bone marrow prompted an examination of B-cell maturation at this latter site. Following a single pulse of BrdU in intact mice, sequential labeling of more mature B-cell populations in the bone marrow suggested ongoing maturation at this site. Further evidence for B-cell maturation in the bone marrow was obtained from analyses of transitional B cells in splenectomized lymphotoxin α-deficient mice that lack all secondary lymphoid organs. In these mice, antibody-secreting cells recognizing multivalent antigens were also observed in the bone marrow following an intravenous microbial challenge. These data suggest that newly formed B cells mature into IgDhi B cells simultaneously in the spleen and the bone marrow and establish in a stringent manner that humoral immune responses can be initiated in situ in the bone marrow.

Distinct roles of BCNP1 in B-cell development and activation

2019 ◽  
Vol 32 (1) ◽  
pp. 17-26
Author(s):  
Rongjian Hong ◽  
Nannan Lai ◽  
Ermeng Xiong ◽  
Rika Ouchida ◽  
Jiping Sun ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Cell Receptor ◽  
Cell Development ◽  
B Cell Development ◽  
Cross Linking ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
B Cell Maturation

Abstract B-cell novel protein 1 (BCNP1) has recently been identified as a new B-cell receptor (BCR) signaling molecule but its physiological function remains unknown. Here, we demonstrate that mice deficient in BCNP1 exhibit impaired B-cell maturation and a reduction of B-1a cells. BCNP1-deficient spleen B cells show enhanced survival, proliferation and Ca2+ influx in response to BCR cross-linking as compared with wild-type spleen B cells. Consistently, mutant B cells show elevated phosphorylation of SYK, B-cell linker protein (BLNK) and PLCγ2 upon BCR cross-linking. In vivo, BCNP1-deficient mice exhibit enhanced humoral immune responses to T-independent and T-dependent antigens. Moreover, aged mutant mice contain elevated levels of serum IgM and IgG3 antibodies and exhibit polyclonal and monoclonal B-cell expansion in lymphoid organs. These results reveal distinct roles for BCNP1 in B-cell development, activation and homeostasis.

scholarly journals The concerted change in the distribution of cell cycle phases and zone composition in germinal centers is regulated by IL-21

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Dimitra Zotos ◽  
Isaak Quast ◽  
Connie S. N. Li-Wai-Suen ◽  
Craig I. McKenzie ◽  
Marcus J. Robinson ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
B Cells ◽  
B Cell ◽  
Cell Cycle Progression ◽  
Affinity Maturation ◽  
Antibody Affinity ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Important Regulator

AbstractHumoral immune responses require germinal centres (GC) for antibody affinity maturation. Within GC, B cell proliferation and mutation are segregated from affinity-based positive selection in the dark zone (DZ) and light zone (LZ) substructures, respectively. While IL-21 is known to be important in affinity maturation and GC maintenance, here we show it is required for both establishing normal zone representation and preventing the accumulation of cells in the G1 cell cycle stage in the GC LZ. Cell cycle progression of DZ B cells is unaffected by IL-21 availability, as is the zone phenotype of the most highly proliferative GC B cells. Collectively, this study characterises the development of GC zones as a function of time and B cell proliferation and identifies IL-21 as an important regulator of these processes. These data help explain the requirement for IL-21 in normal antibody affinity maturation.

scholarly journals The histone methyltransferase DOT1L is essential for humoral immune responses

2019 ◽  
Author(s):  
Liam Kealy ◽  
Andrea Di Pietro ◽  
Lauren Hailes ◽  
Sebastian Scheer ◽  
Lennard Dalit ◽  
...  
Keyword(s):  
Gene Expression ◽  
B Cell ◽  
Cell Biology ◽  
Influenza Infection ◽  
Humoral Response ◽  
Histone Methyltransferase ◽  
B Cell Differentiation ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Histone Modifiers

SUMMARYHistone modifiers are essential molecular regulators that underpin the ability of immune cells to reprogram their gene expression during differentiation. The recruitment of the histone methyltransferase DOT1L induces oncogenic gene expression in a subset of B cell leukemia. Despite its importance, little is known about its role in the humoral immune system. Herein, we demonstrate that DOT1L is a critical regulator of B cell biology. Dot1lf/fMb1Cre/+ mice had a block in B cell development, culminating in a significant reduction of mature B cells in the periphery. Upon immunization or influenza infection of Dot1lf/fCd23Cre/+ mice, germinal centers failed to form and class-switched antibody-secreting cells were significantly attenuated. Consequently, immunized mice revealed that DOT1L was essential for the formation of B cell memory populations. Transcriptome, pathway and histological analysis identified a key role for DOT1L in reprogramming gene expression for migration and localization during the initial stages of a humoral response. Together, these results demonstrate an essential role for DOT1L in antigen-dependent B cell differentiation and hence, in generating an effective and lasting humoral immune response.

scholarly journals The immunosenescence-related factor DOCK11 is involved in secondary immune responses of B cells

2022 ◽  
Vol 19 (1) ◽  
Author(s):  
Yuma Sugiyama ◽  
Mitsuhiro Fujiwara ◽  
Akihiko Sakamoto ◽  
Hiromichi Tsushima ◽  
Akihiko Nishikimi ◽  
...  
Keyword(s):  
B Cells ◽  
Immune Responses ◽  
B Cell ◽  
Germinal Center ◽  
Protein Antigen ◽  
Related Factor ◽  
Limited Information ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
T Cell Help

Abstract Background Memory B cells are an antigen-experienced B-cell population with the ability to rapidly differentiate into antibody-producing cells by recall responses. We recently found that dedicator of cytokinesis 11 (DOCK11) contributes to the expansion of antigen-specific populations among germinal center B cells upon immunization. In comparison, limited information is available on the contribution of DOCK11 to secondary humoral immune responses. Results In this study, effects of the DOCK11 deficiency in B cells were examined on secondary immune responses to protein antigen. The lack of DOCK11 in B cells resulted in the impaired induction of antibody-producing cells upon secondary immunization with protein antigen. DOCK11 was dispensable for the recall responses of antigen-experienced B cells, as demonstrated by the comparable induction of antibody-producing cells in mice given transfer of antigen-experienced B cells with no DOCK11 expression. Instead, the lack of DOCK11 in B cells resulted in the impaired secondary immune responses in a B cell-extrinsic manner, which was recovered by the adoptive transfer of cognate T cells. Conclusions We addressed that intrinsic and extrinsic effects of DOCK11 expression in B cells may contribute to secondary humoral immune responses in manner of the induction of cognate T-cell help.

scholarly journals Effect of nabumetone on humoral immune responses in mice

2020 ◽  
Vol 72 (3) ◽  
pp. 915-920
Author(s):  
Khalid Naveed ◽  
Aqeel Javeed ◽  
Muhammad Ashraf ◽  
Amjad Riaz ◽  
Aamir Ghafoor ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Immune Response ◽  
Immune Responses ◽  
Plaque Formation ◽  
Control Group ◽  
Treatment Groups ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Significant Difference ◽  
Mortality Ratio

ABSTRACT Nabumetone is used to reduce the pain and inflammation in rheumatoid arthritis. In the current study, immunomodulatory effect of Nabumetone is investigated in mice. The control group was administered normal saline orally as placebo. Nabumetone was administered orally via gavage in two treatment groups at 14mg/kg.b.w. doses and 28mg/kgb.w., respectively. Haemagglutination (HA) assay, Jerne hemolytic plaque and mice lethality assays were applied. In HA assay, the titer was significantly decreased in Nabumetone treatment groups (P< 0.001). In Jerne hemolytic plaque formation assay, there was a significant reduction (P< 0.001) in number of plaques in Nabumetone treated groups when compared with control. In mice lethality assay, there was a significant difference in mortality ratio of mice in control and Nabumetone treated groups (P< 0.001). Therefore, it is concluded that Nabumetone suppresses the humoral immune response in mice.

Sign in / Sign up

Export Citation Format

Share Document