Recently identified receptor helps trigger first wave of immune response

February 1, 2013, RIKEN
In wild-type mice, immune stimuli cause B cells (green) to interact with T cells (red) within structures known as germinal centers (left), giving rise to antibody-secreting plasma cells and memory cells that facilitate long-term immunity. In mice lacking FcμR, however, these germinal centers are greatly diminished (right). Blue dye indicates cell nuclei. Credit: 2012 Hiroshi Ohno and Ji-Ying Wang, RIKEN Research Center for Allergy and Immunology

B cells can generate different 'classes' of antibodies, each of which carries a specific type of protein chain that triggers a specific downstream cascade of immune responses. Immunoglobulin M (IgM) antibodies, which are the first on the scene, play a particularly important role in fighting off pathogen infection.

It took scientists nearly 40 years to finally isolate FcμR, a that enables to respond to IgM. Hiroshi Ohno's team at the RIKEN Research Center for Allergy and Immunology (RCAI) in Yokohama was among the first to identify the gene encoding this receptor, and he and his RCAI colleague Ji-Yang Wang recently set out to characterize its function by generating a strain of FcμR-deficient mice.

FcμR is predominantly produced by B cells in mice, and Ohno and Wang did not observe any significant differences in overall B cell numbers in the genetically modified animals. When the researchers triggered an in B cells from these mice, however, they found that these cells divided more slowly and subsequently began dying off. FcμR-deficient mice also generated significantly fewer plasma and memory B cells, which are respectively responsible for antibody secretion and coordinating the immune response to recurring infection. Collectively, these results indicate that although this receptor is not required for B cell maturation, it is likely to play a critical role in mounting the initial immune response in the presence of an infectious threat.

As the FcμR-deficient mice grew older, they produced sharply elevated numbers of antibodies targeting host tissues, similar to those produced in like lupus or . Such 'auto-antibodies' are of the immunoglobulin G (IgG) subtype, which appears later in the immune response relative to IgM, suggesting that FcμR is required for to properly manage the shift from IgM- to IgG-mediated immunity. "Our work defines and closes an auto-regulatory loop that ensures adequate B cell activation during the early phase of an antibody response, yet prevents excess activation at the late phase," explains Wang.

These results do not tell the entire story about IgM signaling, which also employs a parallel network known as the complement pathway, but Wang and Ohno believe their findings could offer clinical opportunities for patients with malfunctions in IgM production as well as other immune disorders. "FcμR might contribute to human chronic lymphocytic leukemia (CLL) and, if so, inhibition of FcμR signaling by inhibitors or blocking antibodies could offer therapeutic benefit," says Ohno.

Explore further: Identification of developmental 'master switch' helps scientists explore function of infection-preventing cells

More information: Ouchida, R., et al. Critical role of the IgM Fc receptor in IgM homeostasis, B-cell survival, and humoral immune responses. Proceedings of the National Academy of Sciences USA 109, E2699–E2706 (2012). www.pnas.org/content/109/40/E2699.abstract

Related Stories

Identification of developmental 'master switch' helps scientists explore function of infection-preventing cells

December 14, 2012
Every bite of food or drink of water is an invitation for potentially harmful bacteria and viruses to set up shop in the body. In order to protect against such invaders, the mucous membrane that lines the intestine contains ...

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, ...

Recommended for you

Novel genomic tools provide new insight into human immune system

January 19, 2018
When the body is under attack from pathogens, the immune system marshals a diverse collection of immune cells to work together in a tightly orchestrated process and defend the host against the intruders. For many decades, ...

Genomics reveals key macrophages' involvement in systemic sclerosis

January 18, 2018
A new international study has made an important discovery about the key role of macrophages, a type of immune cell, in systemic sclerosis (SSc), a chronic autoimmune disease which currently has no cure.

First vaccine developed against grass pollen allergy

January 18, 2018
Around 400 million people worldwide suffer in some form or other from a grass pollen allergy (rhinitis), with the usual symptoms of runny nose, cough and severe breathing problems. In collaboration with the Viennese firm ...

Researchers discover key driver of atopic dermatitis

January 17, 2018
Severe eczema, also known as atopic dermatitis, is a chronic inflammatory skin condition that is driven by an allergic reaction. In their latest study, researchers at La Jolla Institute reveal an important player that promotes ...

Who might benefit from immunotherapy? New study suggests possible marker

January 16, 2018
While immunotherapy has made a big impact on cancer treatment, the fact remains that only about a quarter of patients respond to these treatments.

Researchers identify new way to unmask melanoma cells to the immune system

January 16, 2018
system, which enables these deadly skin cancers to grow and spread.

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.