期刊
JOURNAL OF IMMUNOLOGY
卷 190, 期 1, 页码 106-114出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1200907
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资金
- European Research Council
- Agence Nationale pour la Recherche
- Agence pour la Recherche sur le Cancer
- Institut Pasteur
- Centre National pour la Recherche Scientifique
- INSERM
- Direction Recherche Enseignement et Technologie
- Fundacion Instituto Mediterraneo para el Avance de la Biomedicina y la Investigacion Biosanitaria (Malaga, Spain)
- Fondation de le Recherche Medicale
- National Institutes of Health [RO1 HL72523, R01 101748]
- Paige Arnold Butterfly Run
- Versus Arthritis [19497] Funding Source: researchfish
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL072523] Funding Source: NIH RePORTER
Maintenance of plasma IgM levels is critical for immune system function and homeostasis in humans and mice. However, the mechanisms that control homeostasis of the activated IgM-secreting B cells are unknown. After adoptive transfer into immune-deficient hosts, B lymphocytes expand poorly, but fully reconstitute the pool of natural IgM-secreting cells and circulating IgM levels. By using sequential cell transfers and B cell populations from several mutant mice, we were able to identify novel mechanisms regulating the size of the IgM-secreting B cell pool. Contrary to previous mechanisms described regulating homeostasis, which involve competition for the same niche by cells having overlapping survival requirements, homeostasis of the innate IgM-secreting B cell pool is also achieved when B cell populations are able to monitor the number of activated B cells by detecting their secreted products. Notably, B cell populations are able to assess the density of activated B cells by sensing their secreted IgG. This process involves the Fc gamma RIIB, a low-affinity IgG receptor that is expressed on B cells and acts as a negative regulator of B cell activation, and its intracellular effector the inositol phosphatase SHIP. As a result of the engagement of this inhibitory pathway, the number of activated IgM-secreting B cells is kept under control. We hypothesize that malfunction of this quorum-sensing mechanism may lead to uncontrolled B cell activation and autoimmunity. The Journal of Immunology, 2013, 190: 106-114.
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