Marginal zone B cells acquire dendritic cell functions by trogocytosis

Schriek, Patrick; Ching, Alan; Moily, Nagaraj S.; Moffat, Jessica M; Beattie, Lynette; Steiner, Thiago M.; Hosking, Laine; Thurman, Joshua M.; Holers, Michael; Ishido, Satoshi; Lahoud, Mireille H.; Caminschi, Irina; Heath, William R.; Mintern, Justine D.; Villadangos, José A

doi:10.1126/science.abf7470

Cited by 59 publications

(34 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although trogocytosis or cell fusion can be mistaken as transdifferentiation 27 , 28 , we show that it only accounts for a very minor fraction of B-MF. Instead, the overwhelming majority of B-MF derived from highly FACS-purified CD45.2 + B-cell precursors of the B-cell lineage tracer Mb1-EYFP + mice only expressed CD45.2 after in vitro co-differentiation with CD45.1 + monocyte/macrophages or adoptive transfer in tumor-bearing CD45.1 + mice.…”

Section: Discussionmentioning

confidence: 75%

See 1 more Smart Citation

Cancer co-opts differentiation of B-cell precursors into macrophage-like cells

et al. 2022

View full text Add to dashboard Cite

We have recently reported that some cancers induce accumulation of bone marrow (BM) B-cell precursors in the spleen to convert them into metastasis-promoting, immunosuppressive B cells. Here, using various murine tumor models and samples from humans with breast and ovarian cancers, we provide evidence that cancers also co-opt differentiation of these B-cell precursors to generate macrophage-like cells (termed B-MF). We link the transdifferentiation to a small subset of CSF1R+ Pax5Low cells within BM pre-B and immature B cells responding to cancer-secreted M-CSF with downregulation of the transcription factor Pax5 via CSF1R signaling. Although the primary source of tumor-associated macrophages is monocytes, B-MFs are phenotypically and functionally distinguishable. Compared to monocyte-derived macrophages, B-MFs more efficiently phagocytize apoptotic cells, suppress proliferation of T cells and induce FoxP3+ regulatory T cells. In mouse tumor models, B-MFs promote shrinkage of the tumor-infiltrating IFNγ+ CD4 T cell pool and increase cancer progression and metastasis, suggesting that this cancer-induced transdifferentiation pathway is functionally relevant and hence could serve as an immunotherapeutic target.

show abstract

Section: Discussionmentioning

confidence: 75%

“…Because B-MF could be misinterpreted as trogocytosis or cell fusion 27 , 28 , we performed a series of B-cell differentiation experiments using highly FACS-purified CD19 + B220 + B cells (Lin − , >99% purity, Supplementary Fig. 3a ) from BM of naïve mice.…”

Section: Resultsmentioning

confidence: 99%

Cancer co-opts differentiation of B-cell precursors into macrophage-like cells

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Such organisms also contain T celldependent Ags, and MZB cells can generate Ab responses to them as well, following interaction with T follicular helper or NKT cells. A recent study showed that MZB cells can capture peptideMHC class II complexes from DCs, in a manner that involves binding of complement component C3 with peptideclass II complexes on DCs, followed by plasma membrane transfer to MZB cells via complement receptor 2 in a process called trogocytosis, thus endowing MZB cells with DC-like functions (56). The capacity of MZB cells to generate memory responses remains uncertain.…”

Section: Innate-like B Cellsmentioning

confidence: 99%

Innate and Innate-like Effector Lymphocytes in Health and Disease

Kaer

Postoak

Song

et al. 2022

The Journal of Immunology

View full text Add to dashboard Cite

Lymphocytes can be functionally partitioned into subsets belonging to the innate or adaptive arms of the immune system. Subsets of innate and innate-like lymphocytes may or may not express Ag-specific receptors of the adaptive immune system, yet they are poised to respond with innate-like speed to pathogenic insults but lack the capacity to develop classical immunological memory. These lymphocyte subsets display a number of common properties that permit them to integrate danger and stress signals dispatched by innate sensor cells to facilitate the generation of specialized effector immune responses tailored toward specific pathogens or other insults. In this review, we discuss the functions of distinct subsets of innate and innate-like lymphocytes. A better understanding of the mechanisms by which these cells are activated in different contexts, their interactions with other immune cells, and their role in health and disease may inform the development of new or improved immunotherapies.

show abstract

“…A 2022 report by Schriek et al [11 ▪▪ ] uncovered a novel complement-dependent process that facilitates antigen presentation by marginal zone B cells (MZB) to CD4 + T cells. C3b activation occurs preferentially on glycosylated sites on class II MHC molecules expressed by conventional dendritic cells (cDC), resulting in C3dg opsonization.…”

Section: Complement and B Cellsmentioning

confidence: 99%

Effects of the complement system on antibody formation and function: implications for transplantation

Čumpelik

Heeger²

2022

Current Opinion in Organ Transplantation

View full text Add to dashboard Cite

Purpose of reviewIn antibody-mediated allograft rejection, donor-reactive antibodies cause transplant injury in part via complement activation. New mechanistic insights indicate complement also modulates development of humoral immune responses. Herein we review recent data that describes how complement affects antibody formation and we discuss therapeutic implications.Recent findingsExtravasating T cells interacting with integrins express and activate intracellular complement that drives immune-metabolic adaptations vital for CD4+ helper cells. Marginal zone B cells can acquire intact major histocompatibility complexes from dendritic cells via complement-dependent trogocytosis for presentation to T cells. Activated B cells in germinal centers receive co-stimulatory signals from T-helper cells. These germinal center B cells undergo coordinate shifts in surface complement regulator expression that permit complement receptor signaling on the germinal center B cells required for affinity maturation. The positively selected, high-affinity B cells can differentiate into plasma cells that produce donor-HLA-reactive antibodies capable of ligating endothelial, among other, graft cells. Subsequent sublytic complement attack can stimulate endothelial cells to activate CD4+ and CD8+ T cells, promoting cellular and humoral rejection. Newly developed complement inhibitors are being tested to prevent/treat transplant rejection.SummaryThe complement system influences T-cell, B-cell and endothelial-cell activation, and thereby contributes allograft injury. Emerging therapeutic strategies targeting complement activation have the potential to prevent or abrogate transplant injury and improve transplant outcomes.

show abstract

Marginal zone B cells acquire dendritic cell functions by trogocytosis

Cited by 59 publications

References 46 publications

Cancer co-opts differentiation of B-cell precursors into macrophage-like cells

Cancer co-opts differentiation of B-cell precursors into macrophage-like cells

Innate and Innate-like Effector Lymphocytes in Health and Disease

Effects of the complement system on antibody formation and function: implications for transplantation

Contact Info

Product

Resources

About