Requirement for BAFF and APRIL during B Cell Development in GALT

Yeramilli, Venkata A.; Knight, Katherine L.

doi:10.4049/jimmunol.1000146

Cited by 17 publications

(18 citation statements)

References 62 publications

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“…Our data, thus, support a role for BAFF in the differentiation of immature into transitional B cells both in vitro and in vivo and suggest that a cytokine different from BAFF, or a different BAFF receptor, may also operate in the bone marrow environment to assist this process. A proliferation-inducing ligand (APRIL), hemokinin-1 (HK-1), macrophage migration inhibitory factor (MIF), and thymic stromal lymphopoietin (TSLP) are cytokines expressed in the bone marrow tissue and shown to operate at various B cell developmental stages [26, 96–99]. We found that none of these factors, however, aided the differentiation of immature B cells into transitional B cells in vitro in the absence of BAFF [64] and, thus, are not likely the factors that promote the differentiation of CD23 − transitional B cells in the bone marrow of BAFFR-deficient mice.…”

Section: Cytokine Receptors In the Selection Of Immature B Cellsmentioning

confidence: 99%

Antigen and cytokine receptor signals guide the development of the naïve mature B cell repertoire

et al. 2012

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Immature B cells are generated daily in the bone marrow tissue. More than half of the newly generated immature B cells are autoreactive and bind a self-antigen, while the others are nonautoreactive. A selection process has evolved on the one hand to thwart development of autoreactive immature B cells and, on the other hand, to promote further differentiation of nonautoreactive immature B cells into transitional and mature B cells. These negative and positive selection events are carefully regulated by signals that emanate from the antigen receptor, whether antigen-mediated or tonic, and are influenced by signals that are generated by receptors that bind cytokines, chemokines, and other factors produced in the bone marrow tissue. These signals, therefore, are the predominant driving forces for the generation of a B cell population that is capable of protecting the body from infections while maintaining self-tolerance. Here, we review recent findings from our group and others that describe how tonic antigen receptor signaling and bone marrow cytokines regulate the selection of immature B cells.

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Section: Cytokine Receptors In the Selection Of Immature B Cellsmentioning

confidence: 99%

Antigen and cytokine receptor signals guide the development of the naïve mature B cell repertoire

et al. 2012

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“…Both BAFF and APRIL and their receptors are strongly up-regulated in many autoimmune disorders [3, 6, 7]. Because the clinical features of GVHD are similar to those of autoimmune diseases, the elevated serum concentrations of BAFF and APRIL seen in GVHD may be closely related to the processes underlying its development.…”

Section: Introductionmentioning

confidence: 99%

Clinical significance of B cell-activating factor (BAFF) and a proliferation-inducing ligand (APRIL) in acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation

Kim

Cheong

et al. 2011

Korean J Hematol

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BackgroundBAFF (B cell-activating factor) and APRIL (a proliferation-inducing ligand) are members of the tumor necrosis factor family and promote B cell survival and proliferation. We evaluated the correlation between serum concentration of BAFF or APRIL and severity of acute graft-versus-host disease (GVHD).MethodsFifteen patients who received allogeneic hematopoietic stem transplantation for leukemia and developed acute GVHD were enrolled. We determined serum concentrations of BAFF and APRIL at the onset of the first clinical manifestation of GVHD by enzyme-linked immunosorbent assay.ResultsNine patients had grade 2 acute GVHD, and 6 had grade 3-4 acute GVHD. The BAFF serum concentration was higher in patients with grade 3-4 acute GVHD (1,093.42 in grade 2 vs. 2,171.99 pg/mL in grade 3-4), although the difference was not significant (P=0.077). However, the ratio of BAFF serum concentration to absolute lymphocyte count (ALC) (BAFF/ALC) was significantly higher in patients with grade 3-4 acute GVHD (P=0.045). The APRIL serum concentration and APRIL/ALC ratio showed similar results (P=0.077 and P=0.013, respectively).ConclusionPatients with grade 3-4 acute GVHD had higher BAFF/ALC and APRIL/ALC ratios than patients with grade 2 acute GVHD. These findings suggest that B cells might play an important role in the development of acute GVHD, and that the BAFF and APRIL concentrations in serum might be significant predictive factors for estimating the severity of acute GVHD. Their clinical significance should be further evaluated in a larger patient population.

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“…These authors also found that blocking CD21 signaling inhibited B cell proliferation, possibly reflecting an important role for FDC CD21L in stimulating antibody repertoire diversification in rabbit GALT. In addition, blocking BAFF (and APRIL) signaling in neonatal rabbits with a TACI-Ig fusion protein markedly reduced the size and number of proliferating B cell follicles (46). In vitro studies, however, demonstrated that BAFF primarily promoted survival, rather than proliferation, of appendix B cells.…”

Section: Discussionmentioning

confidence: 99%

Chemokine-Mediated B Cell Trafficking during Early Rabbit GALT Development

Zhai

Volgina

Sethupathi

et al. 2014

The Journal of Immunology

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Microbial and host cell interactions stimulate rabbit B cells to diversify the primary antibody repertoire in gut-associated lymphoid tissues (GALT). B cells at the base of appendix follicles begin proliferating and diversifying their V-(D)-J genes around 1 week of age, ∼5 days after B cells first begin entering appendix follicles, To gain insight into the microbial and host cell interactions that stimulate B cells to diversify the primary antibody repertoire, we analyzed B cell trafficking within follicles during the first week of life. We visualized B cells, as well as chemokines that mediate B cell homing in lymphoid tissues, by in situ hybridization, and examined B cell chemokine receptor expression by flow cytometry. We found that B cells were activated, and began downregulating their BCRs, well before a detectable B cell proliferative region appeared at the follicle base. The proliferative region was similar to germinal center dark zones, in that it exhibited elevated CXCL12 mRNA expression, and B cells that upregulated CXCR4 mRNA in response to signals acquired from select intestinal commensals localized in this region. Our results suggest that, after entering appendix follicles, B cells home sequentially to the FAE, the FDC network, the B cell:T cell boundary and, ultimately, the base of the follicle, where they enter a proliferative program and diversify the primary antibody repertoire.

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Requirement for BAFF and APRIL during B Cell Development in GALT

Cited by 17 publications

References 62 publications

Antigen and cytokine receptor signals guide the development of the naïve mature B cell repertoire

Antigen and cytokine receptor signals guide the development of the naïve mature B cell repertoire

Clinical significance of B cell-activating factor (BAFF) and a proliferation-inducing ligand (APRIL) in acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation

Chemokine-Mediated B Cell Trafficking during Early Rabbit GALT Development

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