Tissue Distribution and Dependence of Responsiveness of Human Antigen-Specific Memory B Cells

Giesecke, Claudia; Frölich, Daniela; Reiter, Karin; Mei, Henrik E.; Wirries, Ina; Kuhly, Rainer; Killig, Monica; Glatzer, Timor; Stölzel, Katharina; Perka, Carsten; Lipsky, Peter E.; Dörner, Thomas

doi:10.4049/jimmunol.1302783

Cited by 72 publications

(74 citation statements)

References 63 publications

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“…4). While this may be considered a low frequency, the median of 0.7% for this group is nonetheless approximately 10-fold higher than frequencies of tetanus toxoid-specific PCs reported following immunization with tetanus toxoid (31). Of note, the approach taken to measure the Env-specific ASC frequencies does not provide information on Env-specificity per Ig isotype and obtaining such information would be technically difficult and require twice or more the number of cells used in the current assay.…”

Section: Resultsmentioning

confidence: 58%

Bone Marrow Plasma Cells Are a Primary Source of Serum HIV-1–Specific Antibodies in Chronically Infected Individuals

Montezuma-Rusca

Moir

Kardava

et al. 2015

The Journal of Immunology

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Several potent and broadly neutralizing antibodies to HIV-1 have been isolated recently from peripheral blood B cells of infected individuals, based on pre-screening of antibody activity in the serum. However, little is known regarding the cells that make the antibodies that circulate in the blood. Accordingly, we investigated the most likely source, the bone marrow, of chronically HIV-1-infected individuals who were not receiving antiretroviral therapy. Increased frequencies of plasma cells, as well as B cell precursors, namely preB-I, preB-II, and decreased frequencies of mature B cells were observed in bone marrow aspirates of these individuals compared to HIV-negative counterparts. Increased frequencies of bone marrow plasma cells are consistent with known hallmarks of HIV-1 infection, namely hypergammaglobulinemia and increased frequencies of peripheral blood plasmablasts. Levels of HIV-1 envelope (Env)-binding and HIV-1-neutralizing antibodies were measured in serum and corresponding frequencies of antibody-secreting or Env-binding cells were measured in the blood (plasmablasts and memory B cells) and in the bone marrow (plasma cells). A strong correlation was observed between serum HIV-1-specific antibodies and Env-specific bone marrow-derived plasma cells, but not circulating plasmablasts or memory B cells. These findings demonstrate that despite HIV-1-induced phenotypic and functional B-cell dysregulation in the peripheral blood and secondary lymphoid tissues, bone marrow plasma cells remain a primary source for circulating HIV-1-specific antibodies in HIV-1-infected individuals.

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Section: Resultsmentioning

confidence: 58%

Bone Marrow Plasma Cells Are a Primary Source of Serum HIV-1–Specific Antibodies in Chronically Infected Individuals

Montezuma-Rusca

Moir

Kardava

et al. 2015

The Journal of Immunology

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“…CD27Ϫ memory B cells have been reported to reside within the tonsil and possibly other secondary lymphoid organs (21,42). Their appear-ance in the circulation of SLE patients may therefore reflect the generalized B cell overactivity that is characteristic of SLE, with overflow of this population into the circulation.…”

Section: Discussionmentioning

confidence: 99%

Increased Frequency of a Unique Spleen Tyrosine Kinase Bright Memory B Cell Population in Systemic Lupus Erythematosus

Fleischer

Giesecke

Mei

et al. 2014

Arthritis & Rheumatology

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Objective. Systemic lupus erythematosus (SLE) is characterized by B cell hyperactivity and autoantibody production. As spleen tyrosine kinase (Syk) is pivotal in B cell activation, these experiments aimed to examine the extent to which Syk was abnormally expressed in SLE B cells and the nature of the B cell subset that differently expressed Syk.Methods. B cells from healthy donors and SLE patients were analyzed by flow cytometry to assess basal expression of Syk and phosphorylated Syk. B cell subsets expressing higher levels of Syk were found, and their detailed phenotype, in vitro differentiation into plasmablasts/plasma cells, and Syk induction by cytokines were determined. Conclusion. SLE patients exhibit an increased frequency of hitherto unknown CD27؊Syk؉؉ memorylike B cells, indicating that intracellular Syk density could distinguish CD27؊ memory B cells from truly naive B cell subsets. Furthermore, the CD27؊Syk؉؉ subset is a candidate for a source of increased plasma cells in SLE.B cell activation is a complex process involving different soluble and cellular components and, most importantly, if antigen-dependent, binding of the antigen to the B cell receptor (BCR). After BCR ligation, reorganization of autoregulatory BCR clusters with recruitment of intracellular kinases and subsequent internalization of the cognate antigen (1) initiate an intracellular signaling cascade by phosphorylation of the associated BCR molecules CD79␣ and CD79␤. In this process, other signaling molecules, such as Lyn, spleen tyrosine kinase (Syk), Bruton's tyrosine kinase (BTK), and phospholipase C␥2 (PLC␥2) are recruited and activated in an ordered manner to fine-tune BCR signaling. After BCR engagement, Syk becomes phosphorylated (tyrosine residues Y 348 and Y 352 ), induced by immunoreceptor tyrosine-based activation motifs (ITAMs) on the cytosolic tail of the BCRϪCD79 complex (2).Several studies have linked the development of murine lupus to abnormalities of BCR-associated signalSupported by the DFG (SFB650 project TP16, SFB633 A14, SPP ImmunoBone DFG Do491/8-2, and DFG project Do491/7-3).

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“…Memory B lymphocytes of the bone marrow have not been analyzed extensively 181, 182. Paramithiotis and Cooper showed a preferential localization of IgM and IgD expressing CD24 low CD10 − B lymphocytes with somatically mutated antibody genes indicative of antigen experience in the bone marrow 182.…”

Section: Memory B Lymphocytes Of the Bone Marrowmentioning

confidence: 99%

“…Tetanus‐specific memory B cells were present in all organs analyzed. They concluded that switched memory B lymphocytes of all organs were part of one, circulating population of memory B lymphocytes 181. However, a comprehensive repertoire analysis of memory B lymphocytes of various organs, with the aim to identify resident memory lymphocytes, has not been performed yet.…”

Section: Memory B Lymphocytes Of the Bone Marrowmentioning

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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Tissue Distribution and Dependence of Responsiveness of Human Antigen-Specific Memory B Cells

Cited by 72 publications

References 63 publications

Bone Marrow Plasma Cells Are a Primary Source of Serum HIV-1–Specific Antibodies in Chronically Infected Individuals

Bone Marrow Plasma Cells Are a Primary Source of Serum HIV-1–Specific Antibodies in Chronically Infected Individuals

Increased Frequency of a Unique Spleen Tyrosine Kinase Bright Memory B Cell Population in Systemic Lupus Erythematosus

Immunological memories of the bone marrow

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