Newly activated antibody-producing immune cells can displace older antibody-synthesizing residents in the bone marrow, according to a report to be published online in Nature Immunology. These findings help explain how individuals, as they age, develop 'immunologic memory' to newly encountered pathogens.
Ken Smith and colleagues show plasma cells -- which make antibodies tailored for specific pathogens -- express a protein called FcgammaRIIb on their surface; and that older plasma cells express more of it than newly generated ones. The group shows that when FcgammaRIIb binds onto the older cells it triggers some of these cells to self destruct and thereby make space for the newly made plasma cells to take up residence in the bone marrow. Here they can produce antibodies against recently encountered pathogens.
The authors suggest that plasma cell expression of this protein provides a feedback mechanism to limit the number of antibody-producing cells in the body, which matches previous correlations showing patients with mutations in FcgammaRIIb have higher risk for antibody-mediated autoimmune diseases. Importantly, Smith's group also show human myeloma cells -- which are a form of cancerous cells arising from plasma cells -- are also sensitive to FcgammaRIIb-induced self destruction. Thus, it might be possible to use FcgammaRIIb-targeted therapies to target both pathogenic autoantibody producing cells and myeloma.
Kenneth Smith (University of Cambridge, UK)
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Jeffrey V. Ravetch (Rockefeller University, New York, NY, USA)
Abstract available online.
(C) Nature Immunology press release.
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