Negative regulation of Plasma cells by CD28 and B7 molecules

CD28 和 B7 分子对浆细胞的负调控

基本信息

批准号：
8513589
负责人：
JOSHY JACOB
金额：
$ 44.57万
依托单位：
EMORY UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-08-15 至 2015-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8513589
关键词：
Adopted Affect Antibodies Antibody Formation Antigens Asthma Autoimmune Diseases Autoimmunity Binding Bird Flu vaccine Bone Marrow CD28 gene Cell Surface Proteins Cell physiology Cells Cellular biology Data Disease Enhancing Antibodies Exhibits Experimental Autoimmune Encephalomyelitis Exposure to Feasibility Studies Health Human Immune response Immune system Immunity Infection Inflammation Influenza A Virus, H1N1 Subtype Influenza A Virus, H5N1 Subtype Interruption Invaded Knowledge Lead Life Ligands Longevity Mediating Mediator of activation protein Modeling Multiple Myeloma Mus Phenotype Plasma Cells Play Production Published Comment Reactive Plasma Cell Regulation Research Proposals Role Serological Serum Signal Transduction Smallpox Vaccine Source Stress Stromal Cells T-Cell Activation T-Lymphocyte Tail Testing Time Vaccines Vietnam Work base immunogenic in vivo influenzavirus knockout gene neutralizing antibody pathogen response seasonal influenza src-Family Kinases

项目摘要

DESCRIPTION (provided by applicant): Exposure to pathogens leads to the sustained production of serum antibodies for a life-time. For instance, humans immunized with smallpox vaccine exhibit stable levels of neutralizing antibodies in their serum for over 75 years. Antibodies are produced by plasma cells and these cells are critical effectors of the humoral immune system both in health (responses to pathogens) and in disease (autoimmunity) and hence, it is important to better understand how these cells are regulated and maintained. CD28 is a cell surface protein that is critical for the activation of na¿ve T cells. Interestingly, CD28is expressed also on plasma cells and multiple myeloma cells. Here we provide evidence that CD28 is expressed on both short-lived as well as long-lived plasma cells in the bone marrow. Very little is known about the function of CD28 on plasma cells. We also demonstrate that short- and long-lived plasma cells also express the ligands for CD28, B7.1 and B7.2. Based upon our compelling preliminary data, our central hypothesis is that CD28/B7 molecules are critical for the regulation of plasma cell function and modulation of this interaction using soluble CD28 or B7 molecules will enhance immune responses in vivo. We will test our central hypothesis by pursuing three specific aims. We will determine the extent to which CD28 (Aim 1) and B7. /B7.2 (Aim 2) affects plasma cell function and longevity and determine whether soluble CD28 or B7 can be used to enhance host immune responses to poorly-immunogenic H5N1 avian influenza vaccine (Aim 3). The proposed work is significant, because upon completion, we will have a better understanding of how CD28 and or B7 molecules modulate function and longevity of plasma cells. This could potentially be used to (a) enhance vaccine-induced Ab responses or (b) down modulate self-reactive plasma cells in autoimmune disorders.

描述（由申请人提供）：接触病原体会导致终生持续产生血清抗体，例如，接种天花疫苗的人在其血清中表现出稳定水平的中和抗体超过 75 年。浆细胞和这些细胞是健康（对病原体的反应）和疾病（自身免疫）中体液免疫系统的关键效应器，因此，更好地了解这些细胞的作用非常重要CD28 是一种细胞表面蛋白，对于 na¿ 的激活至关重要。提示，CD28也在浆细胞和多发性骨髓瘤细胞上表达，我们提供的证据表明CD28在骨髓中的短寿命和长寿命浆细胞上都表达，但对其功能知之甚少。我们还证明，短寿命和长寿命的浆细胞也表达 CD28、B7.1 和 B7.2 的配体。根据我们令人信服的初步数据，我们的中心假设是： CD28/B7 分子对于浆细胞功能的调节至关重要，并且使用可溶性 CD28 或 B7 分子调节这种相互作用将增强体内免疫反应，我们将通过追求三个特定目标来检验我们的中心假设。 CD28（目标 1）和 B7.2（目标 2）影响浆细胞功能和寿命，并确定可溶性 CD28 或 B7 是否可用于增强宿主对免疫原性较差的 H5N1 禽类的免疫反应。流感疫苗（目标 3）。这项工作意义重大，因为完成后，我们将更好地了解 CD28 和/或 B7 分子如何调节浆细胞的功能和寿命。诱导抗体反应或（b）下调自身免疫性疾病中的自身反应性浆细胞。

项目成果

期刊论文数量（2）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

The CD28/B7 pathway: a novel regulator of plasma cell function.

CD28/B7 途径：浆细胞功能的新型调节剂。

DOI：
10.1007/978-1-4614-6217-0_8
发表时间：
2024-09-14
期刊：
Advances in experimental medicine and biology
影响因子：
0
作者：
Modesta N. Njau;Joshy Jacob
通讯作者：
Joshy Jacob

CD28-B7 interaction modulates short- and long-lived plasma cell function.

CD28-B7 相互作用调节短寿命和长寿命浆细胞功能。

DOI：
发表时间：
2012-09-15
期刊：
影响因子：
0
作者：
Njau, Modesta N;Kim, Jin Hyang;Chappell, Craig P;Ravindran, Rajesh;Thomas, Leela;Pulendran, Bali;Jacob, Joshy
通讯作者：
Jacob, Joshy