Breaking News
March 26, 2019 - Mental health issues associated with income inequalities in Indigenous people
March 26, 2019 - Participation in sports linked with fewer depressive symptoms in children
March 26, 2019 - Brain process common to sleep and aging discovered
March 26, 2019 - People under age 50 with hearing loss more likely to misuse alcohol and drugs
March 26, 2019 - People with and without cancer use different dosages of cannabis formulations, study shows
March 26, 2019 - Young people at risk of addiction show differences in key brain region
March 26, 2019 - In virtual exchange, students in California and Lebanon unite to improve refugee health
March 26, 2019 - Trump Administration Changes Course, Asks Court To Strike Down ACA
March 26, 2019 - People with untreated diabetes develop signs of Alzheimer’s disease at a faster rate
March 26, 2019 - Study explains how bright colors evolved and diversified in male guppies
March 26, 2019 - Savings from lower insurance costs of growth hormone drugs not passed on to patients
March 26, 2019 - Study highlights the need to pay more attention on specific nutritional needs of female athletes
March 26, 2019 - Sleep quality varies throughout menstrual cycle in young women
March 26, 2019 - Younger Female Blood Donors Vulnerable to Iron Deficiency
March 26, 2019 - Finding the elusive drinking ‘brake’
March 26, 2019 - Using the Mastermind strategy in brain research
March 26, 2019 - Synthetic biological logic gate could one day be used to modify cellular function
March 26, 2019 - Damage to anxiety-associated brain region heightens monkeys’ defensive response
March 26, 2019 - Researchers uncover large-scale brain patterns and networks which control sleep
March 26, 2019 - Scientific Symposium at LABVOLUTION focuses on key issues in life sciences
March 26, 2019 - Screen time plus snacking could increase risk for metabolic syndrome in teens
March 26, 2019 - Attention, Seniors: Drink More Water and Head Off Disease
March 26, 2019 - Peptide shows promise for protecting kidneys from nephritis
March 26, 2019 - Causes of diabetes decline or disappear when ‘zombie cells’ are removed, shows study
March 26, 2019 - Scientists identify common genetic variants associated with post-stroke recovery
March 26, 2019 - Study finds link between menopause and changes in body composition
March 26, 2019 - Higher levels of sex hormones in older men related to lower biological age
March 26, 2019 - Research links participation in team sports to larger hippocampal volumes in children
March 26, 2019 - Cerveau announces research collaboration agreement with Eisai for novel tau imaging agent
March 26, 2019 - New technique measures frequency of sounds emitted from biological structures
March 26, 2019 - Removal of ‘zombie cells’ alleviates causes of diabetes in obese mice
March 26, 2019 - Women exposed to deepwater horizon oil spill continue to experience PTSD symptoms
March 26, 2019 - Shaping new treatments for tuberculosis
March 26, 2019 - Understanding genetic interactions holds key to new personalized therapies
March 26, 2019 - Nervous system relies on guidance cues for neuronal axons to reach destinations
March 26, 2019 - Altering gut microbiome may be potential treatment option for PCOS
March 26, 2019 - Moleculin Files with FDA for Expedited Approval Pathway for Annamycin
March 26, 2019 - GPs play pivotal role in ensuring success of new Faster Diagnosis Standard for Cancer
March 26, 2019 - New clues discovered to lung transplant rejection
March 26, 2019 - New study offers insight into development of delusions
March 26, 2019 - Children’s ball pits full of pathogenic microbes
March 26, 2019 - Exploring pathophysiological factors that link sleep problems and Alzheimer’s disease
March 26, 2019 - Walking downhill after meals can reduce bone resorption in postmenopausal women with diabetes
March 26, 2019 - USA LESS Issues Voluntary Nationwide Recall of LEOPARD Miracle Honey Due to Presence of Undeclared Sildenafil
March 26, 2019 - CT scan prior to spine fusion finds almost half of patients had undiagnosed osteoporosis
March 26, 2019 - After 2 Apparent Student Suicides, Parkland Grieves Again
March 25, 2019 - Inherited form of rickets improves more with new injectable medicine than conventional therapy
March 25, 2019 - Trastuzumab Tied to Higher Long-Term Risk for Heart Failure
March 25, 2019 - Personal context directly affects CPAP use
March 25, 2019 - Mosquito tracking key to preventing disease outbreaks
March 25, 2019 - Scientists Detect Hidden Signals from Beneficial Bacteria
March 25, 2019 - Treating women with thyroid antibodies with Levothyroxine do not increase live birth rate
March 25, 2019 - Brain area that only processes spoken, not written words identified
March 25, 2019 - Race and ethnicity influence fracture risk in diabetic patients
March 25, 2019 - Researchers report new regenerative medicine approach for treating osteoarthritis of the knee
March 25, 2019 - Exposure to dim light at night may contribute to spread of breast cancer to bones
March 25, 2019 - Benefits of osteoporosis treatment in postmenopausal women outweigh the perceived risks
March 25, 2019 - Researchers find evidence of Cryptosporidium parasite in Minnesota’s public water systems
March 25, 2019 - Three Clues to Raised Risk of Miscarriage
March 25, 2019 - Structured play helps toddlers self-regulate, altering their life course
March 25, 2019 - Translating horror into justice: Stanford psychiatrist advocates for human rights
March 25, 2019 - HORIBA Medical introduces D-Dimer reagent for Yumizen G hemostasis range
March 25, 2019 - Recurrent pregnancy loss may be caused by sperm DNA damage, finds study
March 25, 2019 - Special Collection tracks development of new diagnostic tests for tuberculosis
March 25, 2019 - Air Force develops genetic test to predict mental performance
March 25, 2019 - To abort or not to abort—making difficult choices alone
March 25, 2019 - Computer vision technology could aid ICU care by spotting movement
March 25, 2019 - IONTAS wins ‘Small Business of the Year’ category at Cambridge News Business Excellence Awards 2019
March 25, 2019 - First postpartum depression drug gets FDA nod
March 25, 2019 - Research Recognition Award will help improve lives of young people with absence epilepsy
March 25, 2019 - Bisphosphonates to treat osteoporosis appears to be beneficial for all women
March 25, 2019 - Time-restricted eating may prove to be a dietary intervention against breast cancer
March 25, 2019 - Researchers develop new augmented reality app to assess spatial memory
March 25, 2019 - Dolomite Bio releases new Drop-seq datasets for single-cell RNA sequencing
March 25, 2019 - Hemoglobin A1c blood test may underestimate prevalence of diabetes
March 25, 2019 - Immune system errors linked to development of childhood leukemia
March 25, 2019 - Eating leafy green vegetables may help maintain muscle strength and mobility
March 25, 2019 - BMA secures state-backed clinical negligence indemnity scheme for GP trainees
March 25, 2019 - Biohaven Announces Completion of Pre-NDA Meeting With FDA for Oral CGRP Receptor Antagonist Rimegepant
March 25, 2019 - Adding breakfast to classrooms may have a health downside
Clues to lupus’s autoimmune origins in precursor cells

Clues to lupus’s autoimmune origins in precursor cells

image_pdfDownload PDFimage_print
Autoreactive CD27 – IgD – CXCR5 – CD11c + (DN2) B cells expand in lupus patients — DN2 cells derive from naive cells and are poised to generate plasmablasts — DN2 B cells are hyper-responsive to Toll-like receptor-7 signaling Credit: From Jenks Immunity 2018

In the autoimmune disease systemic lupus erythematosus or SLE, the immune system produces antibodies against parts of the body itself. How cells that produce those antibodies escape the normal “checks and balances” has been unclear, but recent research from Emory University School of Medicine sheds light on a missing link.

Investigators led by Ignacio Sanz, MD, studied blood samples from 90 people living with SLE, focusing on a particular type of B cells. These “DN2” B cells are relatively scarce in healthy people but substantially increased in people with SLE.

People with lupus can experience a variety of symptoms, such as fatigue, joint pain, skin rashes and kidney problems. Levels of the DN2 cells were higher in people with more severe disease or kidney problems. DN2 B cells are thought to be “extra-follicular,” which means they are outside the B cell follicles, regions of the lymph nodes where B cells are activated in an immune response.

“Overall, our model is that a lot of lupus auto-antibodies come from a continuous churning out of new responses,” says postdoctoral fellow Scott Jenks, Ph.D., co-first author of the paper. “There is good evidence that DN2 cells are part of the early B cell activation pathway happening outside B cells’ normal homes in lymph nodes.”

Previous research at Emory has shown that African American women have significantly higher rates of lupus than white women. In the current study, the researchers observed that the frequency of DN2 cells was greater in African American patients. Participants in the study were recruited by Emory, University of Rochester and Johns Hopkins.

Sanz, a Georgia Research Alliance Eminent Scholar, is director of the Lowance Center for Human Immunology and head of the division of rheumatology in the Department of Medicine at Emory University School of Medicine. Co-first authors are Jenks, postdoctoral fellow Kevin Cashman, Ph.D. and Esther Zumaquero-Martinez, Ph.D. at the University of Alabama. The lab of Frances Lund, Ph.D. at University of Alabama, as well as postdoc Urko Marigorta, Ph.D. from Georgia Tech contributed to the paper.

The researchers examined the characteristics of DN2 cells and the patterns of genes turned on in those cells. DN2 cells appear to be precursors to the plasmablasts that produce autoreactive antibodies, which cause so much trouble for people with lupus.

Plasmablasts are an important source of antibodies that help get rid of bacteria or viruses during an infection. But in lupus, subsets of B cells and plasmablasts persist in unhealthy ways. In general, we can think of plasmablasts as weapon factories, and B cells as a library of blueprints for various antibodies/weapons. Understanding where the problem plasmablasts come from can provide clues on how to target them and how to control the disease.

Molecular probing showed that DN2 cells in SLE patients are hypersensitive to activation through TLR7, a pathway by which the immune system senses viral infections. This may be how they get over-expanded, Jenks says.

“Our work provides further support for the importance for TLR7 in lupus pathology,” he says. “Targeting TLR7 might both block the generation of pathological B cells and prevent their subsequent activation and differentiation into plasma cells.”

Previous work in Sanz’s lab had shown that a group of “activated naïve” B cells are precursors to the problem plasmablasts. Those cells are very similar, in their molecular markers, to DN2 cells. Jenks says the researchers are now figuring out the relationship between DN2 and activated naïve cells, as well as investigating additional intervention strategies that could specifically control those cells.


Explore further:
Researchers decode lupus using DNA clues

More information:
Scott A. Jenks et al, Distinct Effector B Cells Induced by Unregulated Toll-like Receptor 7 Contribute to Pathogenic Responses in Systemic Lupus Erythematosus, Immunity (2018). DOI: 10.1016/j.immuni.2018.08.015

Journal reference:
Immunity

Provided by:
Emory University

Tagged with:

About author

Related Articles