Featured Research

from universities, journals, and other organizations

B cells produce antibodies 'when danger calls, but not when it whispers'

Date:
May 15, 2014
Source:
University of California - Los Angeles
Summary:
The immune system's B cells protect us from disease by producing 'smart bullets' that target invaders such as pathogens and viruses. But how do B cells know whether a threat is real and whether to start producing these weapons? An international team of life scientists shows how these cells respond only to true threats.

Mutations in the B cell's key molecular circuit in chickens, shown in green, resulted in ambiguity about whether the threshold, where the 0 line is, had been reached. Without these mutations, there were no such ambiguities, as the blue dots show.
Credit: Japan's RIKEN Center for Integrative Medical Sciences

The immune system's B cells protect us from disease by producing antibodies, or "smart bullets," that specifically target invaders such as pathogens and viruses while leaving harmless molecules alone. But how do B cells determine whether a threat is real and whether to start producing these weapons?

An international team of life scientists shows in the May 16 issue of the journal Science how and why these cells respond only to true threats.

"It is critical for B cells to respond either fully or not at all. Anything in between causes disease," said the study's senior author, Alexander Hoffmann, a professor of microbiology, immunology and molecular genetics in the UCLA College of Letters and Science. "If B cells respond wimpily when there is a real pathogen, you have immune deficiency, and if they respond inappropriately to something that is not a true pathogen, then you have autoimmune disease."

The antibodies produced by B cells attack antigens -- molecules associated with pathogens, microbes and viruses. A sensor on the cell's surface is meant to recognize a specific antigen, and when the sensor encounters that antigen, it sends a signal that enables the body's army of B cells to respond rapidly. However, there may be similar molecules nearby that are harmless. The B cells should ignore their signals -- something they fail to do in autoimmune diseases.

So how do the B cells decide whether to start producing antibodies?

"These immune cells are somewhat hard of hearing, which is appropriate because the powerful and potentially destructive immune responses should jump into action only when danger calls, not when it whispers," said Hoffmann.

The B cells make their response only when a rather high threshold is reached, Hoffmann and his colleagues report. A small or moderate signal -- from a harmless molecule, for instance -- gets no response, which reduces the risk of false alarms.

"It's like your car's airbag, which won't be deployed unless you really need it," Hoffmann said. "You can imagine that if the airbag were poorly designed and if you brake very hard or have a slight accident, it could deploy slowly and be useless. You want it to deploy fully or not at all. That is what the B cell does when deciding whether it confronts something that is truly pathogenic or harmless. No B cell responds partially."

We have billions of B cells, and each one creates this threshold through a molecular circuit involving two molecules. One of these molecules, known as CARMA1, activates the other, IKKb, which further activates the first one.

"Positive feedback between the two causes infinite growth, and once you trigger it, there is no way to turn it off until the smart bullets are shot," said Hoffmann, whose research aims to understand and decode the language of cells. "But a second feature of positive feedback is that it can create a threshold only above which this runaway activation occurs."

He and his colleagues developed mathematical equations based on the molecular circuit and were then able to simulate, virtually, B cell responses. The team's resulting predictions were tested experimentally by their collaborators at the Laboratory for Integrated Cellular Systems at Japan's RIKEN Center for Integrative Medical Sciences. In one part of the study, the researchers made specific mutations in IKKb so that it could not signal back to CARMA1. They also made mutations in CARMA1 to prevent it from receiving the signal from IKKb. In both cases, the B cells responded partially, some of the time, like a weakly inflating airbag.

"It became a gray-zone response rather than a black-and-white response," said Hoffmann, who constructs mathematical models of biology.

The research could lead to better diagnosis of disease if patients with an autoimmune disorder, such as lupus, have a defect in this molecular circuit.


Story Source:

The above story is based on materials provided by University of California - Los Angeles. The original article was written by Stuart Wolpert. Note: Materials may be edited for content and length.


Journal Reference:

  1. H. Shinohara, M. Behar, K. Inoue, M. Hiroshima, T. Yasuda, T. Nagashima, S. Kimura, H. Sanjo, S. Maeda, N. Yumoto, S. Ki, S. Akira, Y. Sako, A. Hoffmann, T. Kurosaki, M. Okada-Hatakeyama. Positive Feedback Within a Kinase Signaling Complex Functions as a Switch Mechanism for NF-B Activation. Science, 2014; 344 (6185): 760 DOI: 10.1126/science.1250020

Cite This Page:

University of California - Los Angeles. "B cells produce antibodies 'when danger calls, but not when it whispers'." ScienceDaily. ScienceDaily, 15 May 2014. <www.sciencedaily.com/releases/2014/05/140515154134.htm>.
University of California - Los Angeles. (2014, May 15). B cells produce antibodies 'when danger calls, but not when it whispers'. ScienceDaily. Retrieved July 29, 2014 from www.sciencedaily.com/releases/2014/05/140515154134.htm
University of California - Los Angeles. "B cells produce antibodies 'when danger calls, but not when it whispers'." ScienceDaily. www.sciencedaily.com/releases/2014/05/140515154134.htm (accessed July 29, 2014).

Share This




More Health & Medicine News

Tuesday, July 29, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Deadly Ebola Virus Threatens West Africa

Deadly Ebola Virus Threatens West Africa

AP (July 28, 2014) West African nations and international health organizations are working to contain the largest Ebola outbreak in history. It's one of the deadliest diseases known to man, but the CDC says it's unlikely to spread in the U.S. (July 28) Video provided by AP
Powered by NewsLook.com
$15B Deal on Vets' Health Care Reached

$15B Deal on Vets' Health Care Reached

AP (July 28, 2014) A bipartisan deal to improve veterans health care would authorize at least $15 billion in emergency spending to fix a veterans program scandalized by long patient wait times and falsified records. (July 28) Video provided by AP
Powered by NewsLook.com
Two Americans Contract Ebola in Liberia

Two Americans Contract Ebola in Liberia

Reuters - US Online Video (July 28, 2014) Two American aid workers in Liberia test positive for Ebola while working to combat the deadliest outbreak of the virus ever. Linda So reports. Video provided by Reuters
Powered by NewsLook.com
Traditional African Dishes Teach Healthy Eating

Traditional African Dishes Teach Healthy Eating

AP (July 28, 2014) Classes are being offered nationwide to encourage African Americans to learn about cooking fresh foods based on traditional African cuisine. The program is trying to combat obesity, heart disease and other ailments often linked to diet. (July 28) Video provided by AP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins