In mice, memory B (Bmem) cells can be divided into two subpopulations: CD80hi Bmem cells, which preferentially differentiate into plasma cells; and CD80lo Bmem cells, which become germinal center (GC) B cells during a recall response. We demonstrate that these distinct responses can be B-cell-intrinsic and essentially independent of B-cell receptor (BCR) isotypes. Furthermore, we find that the development of CD80hi Bmem cells in the primary immune response requires follicular helper T cells, a relatively strong CD40 signal and a high-affinity BCR on B cells, whereas the development of CD80lo Bmem cells does not. Quantitative differences in CD40 stimulation were enough to recapitulate the distinct B cell fate decisions in an in vitro culture system. The quantity of CD40 signaling appears to be translated into NF-κB activation, followed by BATF upregulation that promotes Bmem cell differentiation from GC B cells.
Excretion of 125I labelled polyvinyl pyrrolidine (PVP test) was 2 5% (normal <0 5%), which confirmed the diagnosis of protein losing enteropathy.Oral prednisolone (60 mg/day) was given, and after eight weeks the PVP test was reduced to 0-77% and total protein and albumin became normal. She continues to be well with 10 mg prednisolone every two days, but mild dilatation of the lymphatic vessels in the small intestine still remained 12 weeks after the start of steroid treatment. A 16 year old Japanese girl with a facial rash and fever was admitted to our hospital in September 1982. Pleural effusion, a high titre of antinuclear antibody and anti-DNA antibody, and leucopenia were found and a diagnosis of SLE was made. Treatment with oral prednisolone 60
The longevity of plasma cells is dependent on their ability to access and reside in so-called niches that are predominantly located in the bone marrow. Here, by employing a traceable method to label recently generated plasma cells, we showed that homeostatic plasma cells in the bone marrow and spleen were continuously replenished by newly generated B220hiMHC-IIhi populations that progressively differentiated into B220loMHC-IIlo long-lived plasma cell (LLPC) populations. We also found that, in the bone marrow, germinal center (GC)–independent and GC-dependent plasma cells decayed similarly upon NP-CGG engagement, and both entered the B220loMHC-IIlo LLPC pool. Compared with NP+B220hiMHC-IIhi plasma cells, NP+B220loMHC-IIlo cells were more immobilized in the bone marrow niches and showed better survival potential. Thus, our results suggest that the adhesion status of bone marrow plasma cells is dynamically altered during their differentiation and is associated with provision of survival signals.
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