NF-κB activity marks cells engaged in receptor editing

نویسندگان

  • Emily J. Cadera
  • Fengyi Wan
  • Rupesh H. Amin
  • Hector Nolla
  • Michael J. Lenardo
  • Mark S. Schlissel
چکیده

Because of the extreme diversity in immunoglobulin genes, tolerance mechanisms are necessary to ensure that B cells do not respond to self-antigens. One such tolerance mechanism is called receptor editing. If the B cell receptor (BCR) on an immature B cell recognizes self-antigen, it is down-regulated from the cell surface, and light chain gene rearrangement continues in an attempt to edit the autoreactive specificity. Analysis of a heterozygous mutant mouse in which the NF-kappaB-dependent IkappaB alpha gene was replaced with a lacZ (beta-gal) reporter complementary DNA (cDNA; IkappaB alpha(+/lacZ)) suggests a potential role for NF-kappaB in receptor editing. Sorted beta-gal(+) pre-B cells showed increased levels of various markers of receptor editing. In IkappaB alpha(+/lacZ) reporter mice expressing either innocuous or self-specific knocked in BCRs, beta-gal was preferentially expressed in pre-B cells from the mice with self-specific BCRs. Retroviral-mediated expression of a cDNA encoding an IkappaB alpha superrepressor in primary bone marrow cultures resulted in diminished germline kappa and rearranged lambda transcripts but similar levels of RAG expression as compared with controls. We found that IRF4 transcripts were up-regulated in beta-gal(+) pre-B cells. Because IRF4 is a target of NF-kappaB and is required for receptor editing, we suggest that NF-kappaB could be acting through IRF4 to regulate receptor editing.

برای دانلود رایگان متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

VGB3 Induces Apoptosis by Inhibiting Phosphorylation of NF-κB p65 at Serine 536 in the Human Umbilical Vein Endothelial Cells

Background and objectives: Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) inhibition results in an increase in apoptosis. It has been demonstrated that NF-κB subunit p65 phosphorylation at the IκB kinase phosphorylation site serine 536 (Ser536) is essential for the NF-κB nuclear translocation and activation. Therefore, NF-κB can be downregulated by suppressing its phosph...

متن کامل

Hyperglycemia- Induced NF-κB Activation Increases microRNA-146a Expression in Human Umbilical Vein Endothelial Cells

Background & objectives: Nuclear Factor kappa B (NF-κB), a master switch transcription factor, plays a critical role in the progression and development of hyperglycemia-induced microangiopathy. Hyperglycemia activates NF-κB, and subsequently increases pro-inflammatory cytokines such as TNF-α, IL-6 and IL-1β leading to development of inflammation. Some new studies have revealed the involvement o...

متن کامل

15-Deoxy-Δ12,14-Prostaglandin J2 Protects PC12 cells from LPS-Induced Cell Death Through Nrf2 pathway in PPAR-γ Dependent Manner

Introduction: The inflammatory response requires a coordinated integration of various signaling pathway including cyclooxygenase (COX). COX catalyzes the formation of prostaglandins from arachidonic acid. Among prostaglandins, 15-Deoxy-D12, 14-prostaglandin J2 (15d-PGJ2), an endogenous ligand of Peroxisome proliferator-activated receptor-gamma (PPAR-γ), has been demonstrated to have anti-inflam...

متن کامل

Caspase inhibition in neuroinflammation induced by soluble β amyloid monomer, protects cells from abnormal survival and proliferation, via attenuation of NFқB activity

Introduction: Evidence suggests that neuronal apoptosis in neurodegenerative diseases is correlated with inflammatory reactions. The beneficial or detrimental role of apoptosis in neuroinflammation is unclear. Elucidating this question may be helpful in management of neurodegenerative diseases. Since TNF-α is able to induce apoptosis as well as increased viability of the cells by activation ...

متن کامل

Evaluation of cytotoxicity mechanism of two cyclo-oxygenase-2 inhibitors in leukemia cell line

Introduction: Leukemia is considered one of the main causes of death, and current chemotherapeutic agents are unable to provide optimal responses due to chemo-resistance. Therefore, there is a constant need for new drugs. Cyclooxygenase- 2 (COX-2) inhibitors can be helpful by reducing the necessary dose of routine chemotherapeutic drugs. Herein, we evaluated the cytotoxicity activity as well...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

عنوان ژورنال:

دوره 206  شماره 

صفحات  -

تاریخ انتشار 2009