BAFF and the plasticity of peripheral B cell tolerance

Stadanlick, Jason; Cancro, Michael P.

doi:10.1016/j.coi.2008.03.015

Cited by 75 publications

(63 citation statements)

References 36 publications

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“…21 Failure to compensate after disruption of B-cell homeostasis with an increase in B-cell number or decreased BAFF results in a breach of an "elastic" BAFF B-cell tolerance checkpoint. 49,50 The present study is the first to demonstrate that delayed recovery of B-cell homeostasis and persistence of high BAFF/B-cell ratios are associated with an activated peripheral B-cell pool in human cGVHD.…”

Section: Discussionmentioning

confidence: 99%

Altered B-cell homeostasis and excess BAFF in human chronic graft-versus-host disease

Sarantopoulos¹,

Stevenson

Kim

et al. 2009

Blood

286

353

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Chronic graft-versus-host disease (cGVHD) causes significant morbidity and mortality in patients otherwise cured of malignancy after hematopoietic stem cell transplantation (HSCT). The presence of alloantibodies and high plasma B cell–activating factor (BAFF) levels in patients with cGVHD suggest that B cells play a role in disease pathogenesis. We performed detailed phenotypic and functional analyses of peripheral B cells in 82 patients after HSCT. Patients with cGVHD had significantly higher BAFF/B-cell ratios compared with patients without cGVHD or healthy donors. In cGVHD, increasing BAFF concentrations correlated with increased numbers of circulating pre–germinal center (GC) B cells and post-GC “plasmablast-like” cells, suggesting in vivo BAFF dependence of these 2 CD27+ B-cell subsets. Circulating CD27+ B cells in cGVHD comprised in vivo activated B cells capable of IgG production without requiring additional antigen stimulation. Serial studies revealed that patients who subsequently developed cGVHD had delayed reconstitution of naive B cells despite persistent BAFF elevation as well as proportional increase in CD27+ B cells in the first year after HSCT. These studies delineate specific abnormalities of B-cell homeostasis in patients with cGVHD and suggest that BAFF targeting agents may be useful in this disease.

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Section: Discussionmentioning

confidence: 99%

Altered B-cell homeostasis and excess BAFF in human chronic graft-versus-host disease

Sarantopoulos¹,

Stevenson

Kim

et al. 2009

Blood

286

353

View full text Add to dashboard Cite

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“…Soluble variants of BAFF are the major contributors of its activity, through regulating the survival of B cells (3 ). The importance of BAFF to B cells was confirmed when mice transfected with the gene BAFF manifested excessive lymphocytic proliferation, together with autoantibody production (4 ).…”

mentioning

confidence: 91%

New ELISA for B Cell–Activating Factor

et al. 2009

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“…Most developing B cells do not survive the competition for entry into mature subsets (1,4,5). Negative selection by clonal deletion continues in the periphery as transitional cells that receive a sufficient BCR stimulus undergo apoptosis (2,3,6,7). In addition, accumulating evidence indicates transitional B cells are positively selected following BCR engagement with self-ligand (8)(9)(10)(11)(12)(13)(14)(15).…”

mentioning

confidence: 99%

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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BAFF and the plasticity of peripheral B cell tolerance

Cited by 75 publications

References 36 publications

Altered B-cell homeostasis and excess BAFF in human chronic graft-versus-host disease

Altered B-cell homeostasis and excess BAFF in human chronic graft-versus-host disease

New ELISA for B Cell–Activating Factor

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

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