Plasma cells are not restricted to the CD27+ phenotype:characterization of CD27-CD43+ antibody-secreting cells

Circulating antibody-secreting cells are present in the peripheral blood of healthy individuals reflecting the continued activity of the humoral immune system. Antibody-secreting cells typically express CD27. Here we describe and characterize a small population of antibody-secreting class switched CD19+CD43+ B cells that lack expression of CD27 in the peripheral blood of healthy subjects. In this study, we characterized CD27-CD43+ cells. We demonstrate that class-switched CD27-CD43+ B cells possess characteristics of conventional plasmablasts as they spontaneously secrete antibodies, are morphologically similar to antibody-secreting cells, show downregulation of B cell differentiation markers, and have a gene expression profile related to conventional plasmablasts. Despite these similarities, we observed differences in IgA and IgG subclass distribution, expression of homing markers, replication history, frequency of somatic hypermutation, immunoglobulin repertoire, gene expression related to Toll-like receptors, cytokines, and cytokine receptors, and antibody response to vaccination. Their frequency is altered in immune-mediated disorders. Conclusion: we characterized CD27-CD43+ cells as antibody-secreting cells with differences in function and homing potential as compared to conventional CD27+ antibody-secreting cells.</p

Mechanisms of tolerance induction by costimulation blockade in a mouse model of graft-versus-host disease

Targeting costimulatory interactions between T cells and APC can potenti ally be useful to treat auto-immune diseases and to prevent transplant r ejection. Blocking of these interactions has already been shown to lead to tolerance in several autoimmunity and transplantation models, but the underlying mechanisms are incompletely understood. Here, we targeted tw o particular costimulatory pathways (the CD28 CD80/CD86 and the CD40 - CD40L pathway) and tried to elucidate the mechanisms responsible for pr omoting tolerance when both pathways are blocked. More specifically, we investigated the involvement of regulatory T cells and of deletion of al lo-reactive cells in the induction and maintenance of tolerance after co stimulation blockade. To study the mechanisms responsible for promoting tolerance after costim ulation blockade, a MHC-mismatched parent-in-F1 mouse model of GVHD was developed. Injection of splenocytes from the C57BL/6 parent strain into a sublethally irradiated F1 offspring (C57BL/6xC3H) induced a GVHD chara cterized by severe pancytopenia. Treatment with anti-CD40L mAb and CTLA4 -Ig every three days during three weeks after splenocyte injection preve nted disease development and induced a long lasting state of stable mixe d chimerism (> 120 days). In parallel, host-specific tolerance was achie ved as demonstrated by lack of host-directed allo-reactivity of donor-ty pe T cells both in vitro and in vivo. Chimerism and tolerance were also obtained after transfer of CD25+ cell depleted splenocytes, showing that CD25+ natural Treg cells are not essential for tolerance induction. We further showed that costimulation blockade results in enhanced Treg cell activity at early timepoints (day 6 day 30) after splenocyte transfer . This was demonstrated by the presence of a high percentage of Foxp3+ c ells among donor CD4+ cells in the spleen of treated animals, and the fi nding that isolated donor T cells at an early timepoint (day 30) after s plenocyte transfer displayed suppressive capacity in vitro. When sorted Foxp3- splenocytes were used as donor cells, there was no de novo induct ion of Foxp3+ cells, indicating that the high percentage of Foxp3+ cells among donor cells originated from Foxp3+ cells present in the donor cel l inoculum. At later timepoints (> 30 days after splenocyte transfer), d eletion of host-reactive T cells was found to be a major mechanism respo nsible for tolerance. Finally, we provided evidence that IL-10 is involv ed in the induction of tolerance by costimulation blockade. In the absen ce of IL-10 producing donor cells, costimulation blockade could not prev ent lethal GVHD in most of the recipient animals.status: publishe

Comment on "Pneumococcal polysaccharide vaccination induces polysaccharide-specific B cells in adult peripheral blood expressing CD19(+)CD20(+)CD3(-)CD70(-)CD27(+)IgM(+)CD43(+)CD5(+/-)"

publisher: Elsevier articletitle: Comment on “Pneumococcal polysaccharide vaccination induces polysaccharide-specific B cells in adult peripheral blood expressing CD19+CD20+CD3−CD70−CD27+IgM+CD43+CD5+/−” journaltitle: Vaccine articlelink: http://dx.doi.org/10.1016/j.vaccine.2013.10.058 content_type: simple-article copyright: Copyright © 2013 Elsevier Ltd. All rights reserved.status: publishe

Response: Extended analysis of microarray data does not contradict preplasmablast phenotype of human CD20+CD27+CD43+ cells

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Human CD20+CD43+CD27+CD5- B cells generate antibodies to capsular polysaccharides of Streptococcus pneumoniae

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Age- and serotype-dependent antibody response to pneumococcal polysaccharides

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Comment on "phenotypic analysis of pneumococcal polysaccharide-specific B cells"

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