CD38 low IgG-secreting cells are precursors of various CD38 high-expressing plasma cell populations

Arce, Sergio; Luger, Elke; Muehlinghaus, Gwendolin; Cassese, Giuliana; Hauser, Anja E.; Horst, Alexander; Lehnert, Katja; Odendahl, Marcus; Hönemann, Dirk; Heller, Karl-Dieter; Kleinschmidt, Harald; Berek, Claudia; Dörner, Thomas; Krenn, Veit; Hiepe, Falk; Bargou, Ralf C.; Radbruch, Andreas; Manz, Rudolf A.

doi:10.1189/jlb.0603279

Cited by 86 publications

(83 citation statements)

References 36 publications

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“…Research approaches that identify DECs, or other multidimensional analyses that lack specific-Ag detection reagents, are also suited to the evaluation of adjuvants (37) or vaccine-primed T cell responses. Memory B cells are geared toward the recognition of previously encountered Ag via their sIg receptors and recall responses, and are not specialized for Ab secretion-like PB/PCs, which have downregulated or lost the expression of many surfaces molecules such as Ig, CD20, and HLA-DR (46,75). Therefore, correlations between the proportion of memory B cells and serum Ab titer observed in this study and others (1, 10, 47) are indirect and suggest that circulating Abs arose from the differentiation of Ag-specific memory B cells in + cells, five successive gates were applied using sIgM, sIgG, CD21, CD27, CD22, CD40, CD62L, CD45RA, Bcl-2, and HLA-DR.…”

Section: Discussionmentioning

confidence: 99%

Identification of Vaccine-Altered Circulating B Cell Phenotypes Using Mass Cytometry and a Two-Step Clustering Analysis

Pejoski¹,

Tchitchek²,

Pozo³

et al. 2016

The Journal of Immunology

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Broadening our understanding of the abundance and phenotype of B cell subsets that are induced or perturbed by exogenous Ags will improve the vaccine evaluation process. Mass cytometry (CyTOF) is being used to increase the number of markers that can be investigated in single cells, and therefore characterize cell phenotype at an unprecedented level. We designed a panel of CyTOF Abs to compare the B cell response in cynomolgus macaques at baseline, and 8 and 28 d after the second homologous immunization with modified vaccinia virus Ankara. The spanning-tree progression analysis of density-normalized events (SPADE) algorithm was used to identify clusters of CD20+ B cells. Our data revealed the phenotypic complexity and diversity of circulating B cells at steady-state and significant vaccine-induced changes in the proportions of some B cell clusters. All SPADE clusters, including those altered quantitatively by vaccination, were characterized phenotypically and compared using double hierarchical clustering. Vaccine-altered clusters composed of previously described subsets including CD27hiCD21lo activated memory and CD27+CD21+ resting memory B cells, and subphenotypes with novel patterns of marker coexpression. The expansion, followed by the contraction, of a single memory B cell SPADE cluster was positively correlated with serum anti-vaccine Ab titers. Similar results were generated by a different algorithm, automatic classification of cellular expression by nonlinear stochastic embedding. In conclusion, we present an in-depth characterization of B cell subphenotypes and proportions, before and after vaccination, using a two-step clustering analysis of CyTOF data, which is suitable for longitudinal studies and B cell subsets and biomarkers discovery.

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Section: Discussionmentioning

confidence: 99%

Identification of Vaccine-Altered Circulating B Cell Phenotypes Using Mass Cytometry and a Two-Step Clustering Analysis

Pejoski¹,

Tchitchek²,

Pozo³

et al. 2016

The Journal of Immunology

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“…While their precursors express CD38 at rather low levels, memory plasma cells express high levels of CD38 28, 29. This CD38 is apparently distinct from CD38 on other cells; it is selectively recognized by a plasma cell‐specific antigen receptor of lamprey, because it is dimerized and shows NAD glycohydrolase activity 30.…”

Section: Memory Plasma Cellsmentioning

confidence: 99%

“…This CD38 is apparently distinct from CD38 on other cells; it is selectively recognized by a plasma cell‐specific antigen receptor of lamprey, because it is dimerized and shows NAD glycohydrolase activity 30. Within CD38 high plasma cells of the bone marrow, further diversity has been described regarding expression of other surface molecules 28. Among those CD19 has raised some interest recently as a candidate marker for memory plasma cells maintaining long‐term memories,31, 32 similar to memory CD4 + T lymphocytes of the bone marrow, as will be discussed later 33.…”

Section: Memory Plasma Cellsmentioning

confidence: 99%

Immunological memories of the bone marrow

Chang

Tokoyoda

Radbruch

2018

Immunological Reviews

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SummaryMemory for antigens once encountered is a hallmark of the immune system of vertebrates, providing us with an immunity adapted to pathogens of our environment. Despite its fundamental relevance, the cells and genes representing immunological memory are still poorly understood. Here we discuss the concept of a circulating, proliferating, and ubiquitous population of effector lymphocytes vs concepts of resting and dormant populations of dedicated memory lymphocytes, distinct from effector lymphocytes and residing in defined tissues, particularly in barrier tissues and in the bone marrow. The lifestyle of memory plasma cells of the bone marrow may serve as a paradigm, showing that persistence of memory lymphocytes is not defined by intrinsic “half‐lives”, but rather conditional on distinct survival signals provided by dedicated niches. These niches are organized by individual mesenchymal stromal cells. They define the capacity of immunological memory and regulate its homeostasis.

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“…Ϫ population of ISC, that appeared to be the precursor of CD38 ϩ ISC, was identified in human tonsils (44). These CD38…”

Section: ) the Finding That 1) Cd38mentioning

confidence: 99%

Increased Expression of CD27 on Activated Human Memory B Cells Correlates with Their Commitment to the Plasma Cell Lineage

Avery

Ellyard

Mackay

et al. 2005

The Journal of Immunology

123

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Plasma cells (PC) or Ig-secreting cells (ISC) are terminally differentiated B cells responsible for the production of protective Ig. ISC can be generated in vitro by culturing human B cells with the T cell-derived stimuli CD40L, IL-2, and IL-10. ISC have traditionally been identified by the increased expression of CD38, analogous to primary human PC, and the acquired ability to secrete Ig. By tracking the proliferation history of activated B cells, we previously reported that the differentiation of memory B cells into CD38+ B cells is IL-10 dependent, and increases in frequency with cell division. However, <50% of CD38+ cells secreted Ig, and there was a population of CD38− ISC. Thus, the PC phenotype of CD38+ cells generated in vitro did not correlate with PC function. To address this, we have examined cultures of activated memory B cells to accurately identify the phenotype of ISC generated in vitro. We found that CD27 is also up-regulated on memory B cells in an IL-10-dependent and division-dependent manner, and that ISC segregated into the CD27high subset of activated memory B cells irrespective of the acquired expression of CD38. The ISC generated in these cultures expressed elevated levels of the transcription factors Blimp-1 and X box-binding protein-1 and reduced levels of Pax-5, and exhibited selective migration toward CXCL12, similar to primary PC. We propose that the differentiation of memory B cells into PC involves a transitional stage characterized by a CD27highCD38− phenotype with the acquired ability to secrete high levels of Ig.

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CD38 low IgG-secreting cells are precursors of various CD38 high-expressing plasma cell populations

Cited by 86 publications

References 36 publications

Identification of Vaccine-Altered Circulating B Cell Phenotypes Using Mass Cytometry and a Two-Step Clustering Analysis

Identification of Vaccine-Altered Circulating B Cell Phenotypes Using Mass Cytometry and a Two-Step Clustering Analysis

Immunological memories of the bone marrow

Increased Expression of CD27 on Activated Human Memory B Cells Correlates with Their Commitment to the Plasma Cell Lineage

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