Detection and characterization of plasma cells in peripheral blood: correlation of IgE+ plasma cell frequency with IgE serum titre

Horst, Alexander; Hunzelmann, Nicolas; Arce, Sergio; Herber, Manuela; Manz, Rudolf A.; Radbruch, Andreas; Nischt, Roswitha; Schmitz, Jürgen; Assenmacher, Mario

doi:10.1046/j.1365-2249.2002.02025.x

Cited by 69 publications

(66 citation statements)

References 59 publications

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“…16 Splenic and BM CD38 ϩϩ CD20 Ϯ B cells expressed elevated levels of CD27, CD31, and CD95 compared with naive and memory B cells (Figure 4), consistent with some recent observations on PCs in human tonsils, PB, and gut. 16,18,19,44,64 Our findings of increased CD27 expression on splenic CD38 ϩϩ CD20 Ϯ B cells were also consistent with our previous observation of intracellular IgM hi CD27 hi cells in the red pulp of human spleen. 26 Overall, based on the expression of the molecules examined in this study, the phenotype of splenic ISCs was more similar to that of tonsillar ISCs rather than ISCs detected in PB or BM.…”

Section: Discussionsupporting

confidence: 81%

Antigen-selected, immunoglobulin-secreting cells persist in human spleen and bone marrow

Ellyard

Avery

Phan

et al. 2004

Blood

128

159

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IntroductionPlasma cells (PCs) are terminally differentiated immunoglobulin (Ig)-secreting cells (ISCs) responsible for humoral immunity. [1][2][3] ISCs can arise from several differentiation pathways. During the extrafollicular reaction, some antigen (Ag)-specific naive B cells undergo rapid clonal expansion and differentiate into ISCs. 1,4,5 Many extrafollicular ISCs are short-lived and secrete either IgM or downstream isotypes. 6,7 The V H genes of extrafollicular ISCs typically remain in their germline configuration, 4,8 indicating they have not undergone significant somatic mutation. Naive B cells can also give rise to ISCs by way of the germinal center (GC) reaction. It is within GC that antigen-specific naive B cells undergo proliferation, somatic mutation of Ig V region genes, Ig isotype switching, and affinity maturation. 1,4,5 Antigen-selected GC B cells can differentiate into ISCs, 5,9,10 most of which migrate to the bone marrow (BM) and become long-lived PCs, whereas a small proportion remains in the spleen. 2,3,7,9,11,12 At the same time, some GC B cells develop into memory B cells, 4,5,10 which can subsequently yield ISCs directly after repeated exposure to an immunizing antigen. 13,14 Thus, the GC reaction serves to expand and diversify the B-cell repertoire, producing high-affinity variants for the long-term maintenance of protective immunity.Most studies examining PCs have been performed using spleens and BM from immunized rodents. However, for a complete understanding of human PC differentiation, and, more important, human diseases characterized by the expansion or transformation of ISCs, it is necessary to examine the human counterpart of these cells directly. Human ISCs can be identified by an up-regulation in expression of CD38 and a concomitant down-regulation of CD20. 15 Based on this phenotype, significant numbers have been detected in BM and peripheral blood (PB) 15,16 and in mucosa-associated lymphoid tissue such as tonsils and gut, [17][18][19] where they usually constitute a very small proportion of mononuclear cells (MNCs; less than 0.1%-1.0%). 15,17,20,21 Although ISCs in human tonsils, PB, and BM have been extensively characterized, 16,17,[20][21][22][23][24][25] ISCs in human spleen have not been reported. Given the identification of a population of long-lived murine splenic PCs, we hypothesized that an analogous population would exist in humans and that this population could contribute to the maintenance of long-term humoral immunity. In this paper we report the identification of a population of human splenic CD38 ϩϩ CD20 Ϯ cells that exhibited many characteristics of BM PCs, and we propose that these cells in human spleen represent an important population of ISCs. Identifying human splenic ISCs will contribute to our understanding of the role played by these cells in normal humoral immunity and of human diseases characterized by B-cell hyperactivity or deficiency. Materials and methods ReagentsThe following monoclonal antibodies (mAbs) were used in this study: fluorescein isothi...

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Section: Discussionsupporting

confidence: 81%

Antigen-selected, immunoglobulin-secreting cells persist in human spleen and bone marrow

Ellyard

Avery

Phan

et al. 2004

Blood

128

159

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“…8 and 9). Our finding of B cells with RV-sIg and the phenotype of ASC is in agreement with previous studies that showed that circulating B cells with intracellular Ig (ASC) also have sIg (15). Nonetheless, ASC have less sIg than B cells that do not have intracellular immunoglobulin (15).…”

Section: Cd38supporting

confidence: 82%

“…Most of our knowledge regarding the phenotype of human ASC and memory B cells comes from the study of non-antigenspecific populations (16,28,31,33). Most of these studies have been done with cells from healthy adults, adults with reactive plasmacytosis (16), allergic patients (15), and patients with autoimmunity (31). Nonetheless, the phenotype that we have described for RV ASC and memory B cells from RV-infected children is generally in agreement with these previous studies.…”

Section: Vol 78 2004 Phenotype Of Children's Rotavirus-specific B Csupporting

confidence: 78%

Maturation and Trafficking Markers on Rotavirus-Specific B Cells during Acute Infection and Convalescence in Children

Jaimes

Rojas

Kunkel³

et al. 2004

J Virol

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most likely representing RVspecific memory B cells with both gut and systemic trafficking profiles. Of note, during acute RV infection both total and RV-specific murine IgM and IgA antibody-secreting cells migrate efficiently to CCL28 (the CCR10 ligand) and to a lesser extent to CCL25 (the CCR9 ligand).Our results show that CCR10 and CCR9 can be expressed on IgM as well as IgA antibody-secreting cells in response to acute intestinal infection, likely helping target these cells to the gut. However, these intestinal infection-induced plasmablasts lack the CLA homing receptor for skin, consistent with mechanisms of differential CCR10 participation in skin T versus intestinal plasma cell homing. Interestingly, RV memory cells generally lack CCR9 and CCR10 and instead express CCR6, which may enable recruitment to diverse epithelial sites of inflammation.

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“…Human PC express a higher level of CD27 than memory B cells (3,6,9,14,33). Therefore, it was of interest to investigate the expression of CD27 on memory B cells cultured under conditions that induce their proliferation and differentiation to CD38 ϩ B cells, which contain a population of ISC.…”

Section: Cd27 Is Up-regulated On Activated Human Memory B Cells In VImentioning

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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Detection and characterization of plasma cells in peripheral blood: correlation of IgE+ plasma cell frequency with IgE serum titre

Cited by 69 publications

References 59 publications

Antigen-selected, immunoglobulin-secreting cells persist in human spleen and bone marrow

Antigen-selected, immunoglobulin-secreting cells persist in human spleen and bone marrow

Maturation and Trafficking Markers on Rotavirus-Specific B Cells during Acute Infection and Convalescence in Children

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

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