It has been proposed that plasma cells specific for previously encountered antigens are maintained in the bone-marrow niche because immunization results in the activation of memory B cells in an antigen-non-specific manner (known as bystander activation) and these cells then contribute to the long-lived plasma-cell population maintained in the bone marrow. To address this, Smith and colleagues immunized mice with the hapten nitrophenol coupled to chicken γ-globulin. The number of plasma cells specific for nitrophenol was assessed after 9 weeks. When the mice were then immunized with a cocktail of non-specific antigens and the frequency of nitrophenol-specific plasma cells was analysed at 15 weeks, there were fewer nitrophenol-specific plasma cells present in the bone marrow than at the 9-week stage. This indicates that bystander activation actually results in decreased numbers of bone-marrow plasma cells.
What could be the explanation for this reduction? Smith and colleagues focused their attention on FcγRIIb, a low-affinity inhibitory receptor for the Fc portion of IgG, as mice deficient in FcγRIIb have more plasma cells than wild-type mice and crosslinking of FcγRIIb induces apoptosis in naive B cells. FcγRIIb was expressed by splenic plasma cells and long-lived plasma cells, and its expression levels were higher on more fully differentiated cells. Abnormal persistence of bone-marrow plasma cells was observed in mice deficient in FcγRIIb, and overexpression of FcγRIIb in transgenic mice reversed this persistence. Furthermore, crosslinking of FcγRIIb resulted in antigen-independent apoptosis of plasma cells, including long-lived plasma cells, which are notoriously difficult to kill. Bone-marrow plasma cells from mice prone to the autoimmune disease systemic lupus erythematosus (SLE) do not express FcγRIIb and therefore these cells could not be killed by crosslinking of FcγRIIb. Failure of FcγRIIb-mediated apoptosis might therefore contribute to the increased number of plasma cells in mice with SLE.
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