Translational Mini-Review Series on B cell subsets in disease. Reconstitution after haematopoietic stem cell transplantation – revelation of B cell developmental pathways and lineage phenotypes

Bemark, Mats; Holmqvist, Joel; Abrahamsson, Jonas; Mellgren, Karin

doi:10.1111/j.1365-2249.2011.04469.x

Cited by 56 publications

(62 citation statements)

References 118 publications

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“…Thus, an important implication of our findings is that CD40-mediated shaping of the mature BCR repertoire may facilitate efficient humoral immune responses to neoantigens. Consistent with this idea, many patients have poor responses to pneumococcal vaccines following BM transplant, despite having reconstituted normal B cell numbers, and T cell targeting to mitigate graft-versus-host disease further exaggerates this defect (53). In addition, the altered BCR repertoire generated in the absence of CD40 signals may promote autoimmunity because hyper-IgM patients lacking CD40L suffer from various autoimmune symptoms (54).…”

Section: /2mentioning

confidence: 64%

CD4+ T Cells and CD40 Participate in Selection and Homeostasis of Peripheral B Cells

Schwartz

Kolhatkar

Thouvenel

et al. 2014

The Journal of Immunology

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Control of peripheral B cell development and homeostasis depends critically on coordinate signals received through the BAFFRs and BCRs. The extent to which other signals contribute to this process, however, remains undefined. We present data indicating that CD4+ T cells directly influence naive B cell development via CD40 signaling. Loss of CD4+ T cells or CD40–CD40L interaction leads to reduced B cell homeostatic proliferation and hindered B cell reconstitution posttransplantation. Furthermore, we demonstrate that in the absence of CD40 signals, these events are modulated by BCR self-reactivity. Strikingly, murine models lacking CD40 reveal a broadly altered BCR specificity and limited diversity by both single-cell cloning and high-throughput sequencing techniques. Collectively, our results imply that any setting of T cell lymphopenia or reduced CD40 function, including B cell recovery following transplantation, will impact the naive B cell repertoire.

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Section: /2mentioning

confidence: 64%

CD4+ T Cells and CD40 Participate in Selection and Homeostasis of Peripheral B Cells

Schwartz

Kolhatkar

Thouvenel

et al. 2014

The Journal of Immunology

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“…One limitation of this study is that the combination of CD24 and CD38 was not included in the flow cytometry panel, because these markers have been acknowledged to distinguish different peripheral B cell maturational stages in humans after the FARMFLORA study was initiated in 2004 (7,8). However, with the use blood samples from healthy unselected children and adults, we sought to examine whether CD5 in combination with CD24 and CD38 could verify that CD5 + B cells were immature/ naive.…”

Section: Discussionmentioning

confidence: 99%

“…After the FARMFLORA study was initiated, cell-surface expression of CD24 in combination with CD38 has been acknowledged to distinguish different human B cell maturational stages in the periphery (7,8). Thus, we examined whether the expression of CD24 and CD38 could verify that the CD5 + B cells in blood samples from unselected healthy newborn children, 7-y-old children, and healthy adults were immature/naive B cells.…”

Section: Cd5 + B Cells Are Of An Immature/naive Phenotypementioning

confidence: 99%

“…The current model for human peripheral B cell development involves five major stages: immature transitional B cells that are recent bone marrow emigrants, mature naive B cells, actively engaged germinal center B cells, memory B cells, and Ig-secreting plasma cells (7). Expression of CD24 in combination with CD38 is now acknowledged to distinguish human peripheral B cell maturational stages, that is, CD24 hi CD38 hi immature transitional cells, CD24 + CD38 + naive cells, and CD24 hi CD38 neg memory cells (8)(9)(10).…”

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confidence: 99%

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High Proportion of CD5+ B Cells in Infants Predicts Development of Allergic Disease

Lundell

Johansen

Adlerberth

et al. 2014

The Journal of Immunology

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Delayed maturation of the immune system has been proposed to be a risk factor for development of allergy, but B cell maturation in relation to allergic disease has not been examined. B cells lose CD5 and acquire CD27 during maturation from immature via mature/naive to Ig-secreting cells and memory cells. We sought to investigate B cell maturation in relation to development of allergic disease and sensitization in the FARMFLORA birth cohort including 65 Swedish children. Total B cell numbers, proportions of CD5+ and CD27+ B cells, and levels of IgM, IgG, IgA, and IgE were measured in blood on repeated occasions from birth to 36 mo of age, and related to allergic disease and sensitization at 18 and 36 mo of age with multivariate discriminant analysis. We also compared the expression of CD24 and CD38 within CD5+ and CD5neg B cells in children and in adults. We found that infants with a high proportion of CD5+ B cells at birth and at 1 mo of age had an increased risk for having allergic disease at 18 and 36 mo of life. Further, the proportions of CD5+ B cells at 1 mo of age were inversely correlated with total IgG levels at 18 and 36 mo of age. The majority of the CD5+ B cells were of a CD24hi/+CD38hi/+ immature/naive phenotype at birth (97%), 7 y of age (95%), and in adults (86%). These results suggest that development of allergic disease is preceded by an immaturity in neonatal B cell phenotype.

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“…11 BM-emigrating transitional B cells appear in blood within the first months after allo-HSCT and are progressively replaced with recovering naïve B cells. 12,13 Germinal-center (GC) defects contribute to the slow regeneration of isotype-class switched CD27 1 memory B cells, which correlates with long-term antibody class deficiencies in some patients.…”

Section: Introductionmentioning

confidence: 99%

Bone marrow T-cell infiltration during acute GVHD is associated with delayed B-cell recovery and function after HSCT

Mensen

Jöhrens

Anagnostopoulos

et al. 2014

Blood

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Key Points• Donor T-cell infiltration of the bone marrow is associated with impaired B-cell immunity after allogeneic HSCT.• Quantification of k-deleting recombination excision circles as a biomarker for bone marrow B-cell output in different clinical episodes.B-cell immune dysfunction contributes to the risk of severe infections after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Delayed B-cell regeneration is found in patients with systemic graft-versus-host disease (GVHD) and is often accompanied by bone marrow (BM) suppression. Little is known about human BM GVHD. We analyzed the reconstitution kinetics of B-cell subsets in adult leukemic patients within 6 months after allo-HSCT. B-cell deficiency already existed before transplant and was aggravated after transplant. Onset of B-cell reconstitution characterized by transitional B-cell recovery occurred either early (months 2-3) or late (from month 6 on) and correlated highly positively with reverse transcription-polymerase chain reaction quantified numbers of k-deleting recombination excision circles (KRECs). Delayed recovery was associated with systemic acute GVHD and full-intensity conditioning therapy. Histological analysis of BM trephines revealed increased T-cell infiltration in late recovering patients, which was associated with reduced numbers of osteoblasts. Functionally, late recovering patients displayed less pneumococcal polysaccharide-specific immunoglobin M-producing B cells on ex vivo B-cell activation than early recovering patients. Our results provide evidence for acute BM GVHD in allo-HSCT patients with infiltrating donor T cells and osteoblast destruction. This is associated with delayed B-cell reconstitution and impaired antibody response. Herein, KREC appears suitable to monitor BM B-cell output after transplant. (Blood. 2014;124(6):963-972)

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Translational Mini-Review Series on B cell subsets in disease. Reconstitution after haematopoietic stem cell transplantation – revelation of B cell developmental pathways and lineage phenotypes

Cited by 56 publications

References 118 publications

CD4+ T Cells and CD40 Participate in Selection and Homeostasis of Peripheral B Cells

CD4+ T Cells and CD40 Participate in Selection and Homeostasis of Peripheral B Cells

High Proportion of CD5+ B Cells in Infants Predicts Development of Allergic Disease

Bone marrow T-cell infiltration during acute GVHD is associated with delayed B-cell recovery and function after HSCT

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