'Rapid response' pathway for immune cell development may improve body's ability to fight recurring infectious threats

February 15, 2013
Fluorescent labeling reveals that both conditionally Bcl6-deficient (top) and wild-type (bottom) mice are able to produce functional memory cells (left column, arrowheads). However, these genetically-modified animals lack germinal center (GC) B cells (right column, yellow), revealing a GC-independent pathway for memory cell development. Credit: 2012 Toshitada Takemori, RIKEN Research Center for Allergy and Immunology

Efficient immune protection requires the ability to rapidly recognize intruders that the body has encountered in the past. This is achieved via 'memory' B cells, which develop following immune system activation by a virus, bacterium or other threat.

"Scientists have known about immunological memory for centuries," explains Toshitada Takemori of the RIKEN Research Center for Allergy and Immunology in Yokohama, "but certain critical aspects of this process remain incompletely defined." As a case in point, Takemori's team and Klaus Rajewsky at Germany's Max-Delbrück-Center for Molecular Medicine recently uncovered striking proof of a novel memory B cell production pathway with a potentially distinct role in .

The initial appearance of an immunity-triggering antigen fuels interaction between B and , which in turn yields activated . These can either differentiate into cells that produce antibodies against the or migrate to structures called 'germinal centers' (GCs) where their antibody-encoding genes undergo extensive mutation. This somatic hypermutation (SHM) process generates antibodies with optimized target affinity and specificity, and the resulting cells mature into antibody-secreting or memory B cells.

However, Takemori has observed evidence that some memory B cells never undergo SHM, apparently developing via a GC-independent pathway. This has proven difficult to verify experimentally: mice lacking the Bcl6 gene fail to develop GCs but also suffer other defects, making them a poor research model. To overcome this, the researchers engineered rodents where Bcl6 inactivation is limited to a subset of relevant cells.

These animals lacked GCs, but nevertheless generated memory B cells after an immune challenge in numbers roughly equivalent to normal mice. Closer examination confirmed that the memory B cells produced by conditionally Bcl6-deficient animals did not undergo SHM. The researchers also isolated non-mutated memory B cells from wild-type animals, although these were eventually outnumbered by mutated memory B cells, indicating that these non-mutated cells represent a distinct subset of memory B cells that develop in advance of the GC maturation process. "Our analysis indicates that immunological memory is established as soon as possible after the onset of immune response," says Takemori.

As non-GC memory B cells produce relatively low-specificity antibodies, the researchers hypothesize that these cells may complement optimized, post-SHM memory B cells by broadly responding to related but distinct threats: for example, influenza viruses in general rather than one specific strain. "We are now determining whether the GC-independent memory pathway assists the GC-dependent pathway to protect hosts against viral infections," says Takemori.

Explore further: Ensuring the persistence of immune memory

More information: Kaji, T., et al. Distinct cellular pathways select germline-encoded and somatically mutated antibodies into immunological memory. Journal of Experimental Medicine 209, 2079–2097 (2012). jem.rupress.org/content/209/11/2079

Takahashi, Y., Ohta, H. & Takemori, T. Fas is required for clonal selection in germinal centers and the subsequent establishment of the memory B cell repertoire. Immunity 14, 181–192 (2001). www.cell.com/immunity/abstract … -7613%2801%2900100-5

Related Stories

Ensuring the persistence of immune memory

September 16, 2011
Structures within the lymph nodes known as germinal centers (GCs) help the body to maintain long-term immune defense against foreign threats. The GCs essentially act as sites where antibody-producing B cells undergo a process ...

How defects in a signaling protein sabotage the immune system in multiple, seemingly contradictory ways

November 21, 2012
The antibody response to immune threats is managed by cells known as B lymphocytes. The differentiation and function of B cells are tightly regulated to ensure a prompt response to confirmed dangers, such as viruses or bacteria, ...

Lasting T cell memories

March 5, 2012
The generation of new memories in the human immune system doesn't come at the cost of old ones, according to a study published on March 5th in the Journal of Experimental Medicine.

Can we all just get along? Immunological memory learns tolerance

January 15, 2013
(Medical Xpress)—Immunology researchers at the University of Connecticut Health Center are learning more about memory T cells, which are cells that fight infection from a previously encountered antigen.

Awaiting orders to retaliate

June 24, 2011
(Medical Xpress) -- When immune system B cells are alerted to the presence of a threat within the body, they form structures called germinal centers, which serve as ad hoc headquarters for marshaling a targeted immune response. ...

New memory for HIV patients

March 26, 2012
The hallmark loss of helper CD4+ T cells during human immunodeficiency virus (HIV) infection may be a red herring for therapeutics, according to a study published on March 26th in the Journal of Experimental Medicine.

Recommended for you

Want to win at sports? Take a cue from these mighty mice

July 20, 2017
As student athletes hit training fields this summer to gain the competitive edge, a new study shows how the experiences of a tiny mouse can put them on the path to winning.

'Smart' robot technology could give stroke rehab a boost

July 19, 2017
Scientists say they have developed a "smart" robotic harness that might make it easier for people to learn to walk again after a stroke or spinal cord injury.

Engineered liver tissue expands after transplant

July 19, 2017
Many diseases, including cirrhosis and hepatitis, can lead to liver failure. More than 17,000 Americans suffering from these diseases are now waiting for liver transplants, but significantly fewer livers are available.

Lunatic Fringe gene plays key role in the renewable brain

July 19, 2017
The discovery that the brain can generate new cells - about 700 new neurons each day - has triggered investigations to uncover how this process is regulated. Researchers at Baylor College of Medicine and Jan and Dan Duncan ...

New animal models for hepatitis C could pave the way for a vaccine

July 19, 2017
They say that an ounce of prevention is worth a pound of cure. In the case of hepatitis C—a disease that affects nearly 71 million people worldwide, causing cirrhosis and liver cancer if left untreated—it might be worth ...

Omega-3 fatty acids fight inflammation via cannabinoids

July 18, 2017
Chemical compounds called cannabinoids are found in marijuana and also are produced naturally in the body from omega-3 fatty acids. A well-known cannabinoid in marijuana, tetrahydrocannabinol, is responsible for some of its ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.