Lin28b promotes fetal B lymphopoiesis through the transcription factor Arid3a

Zhou, Yan; Li, Yuesheng; Bandi, Srinivasa Rao; Tang, Lingjuan; Shinton, Susan A.; Hayakawa, Kyoko; Hardy, Richard R.

doi:10.1084/jem.20141510

Cited by 114 publications

(154 citation statements)

References 34 publications

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“…In contrast, a Lin28b − Let-7 + B lineage precursor becomes predominate in adult B-2 cell development, and mature CD5 + B cell generation declines (1, 2). In humans, Lin28b + Let7 − cells also predominate at the fetal hematopoietic stage as compared to adult (1), resulting in a large proportion of CD5 + B cells in fetal lymphoid tissues and in cord blood (3, 4), whereas CD5 + B cells decline in postnatal development.…”

Section: Introductionmentioning

confidence: 99%

Early Generated B-1–Derived B Cells Have the Capacity To Progress To Become Mantle Cell Lymphoma–like Neoplasia in Aged Mice

Hayakawa

Formica

Nakao

et al. 2018

The Journal of Immunology

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In mice, fetal/neonatal B-1 cell development generates CD5+ B cells (B1a) with autoreactivity. We analyzed B1a cells at the neonatal stage in a VH11/D/JH knock-in mouse line (VH11t) that generates an autoreactive anti-phosphatidylcholine (aPtC) B cell receptors (BCR). Our study revealed that aPtC B1a cells develop in liver, mature in spleen, and distribute in intestine/colon, mesenteric lymph node (mLN) and body cavity, as the outcome of B-1 cell development before B-2 cell development. Throughout life, self-renewing B-1 B1a cells circulate through intestine, mesenteric vessel and blood. The body cavity-deposited B1a cells also re-migrate. In old age, some B1a cells proceed to monoclonal B cell lymphocytosis. When neonatal B-1 B1a cells express an anti-thymocyte/Thy-1 autoreactivity (ATA) BCR transgene in the C.B17 mouse background, ATA B cells increase in PBL and strongly develop lymphomas in aging mice that feature splenomegaly and mLN hyperplasia with heightened expression of CD11b, IL-10, and activated Stat3. At the adult stage, ATA B cells were normally present in the mantle zone area, including in intestine. Furthermore, frequent association with mLN hyperplasia suggests the influence by intestinal microenvironment on lymphoma development. When cyclin D1 was overexpressed by the Eμ-cyclin D1 transgene, ATA B cells progressed to further diffused lymphoma in aged mice, including in various lymph nodes with accumulation of IgMhiIgDloCD5+CD23−CD43+ cells, resembling aggressive human mantle cell lymphoma (MCL). Thus, our findings reveal that early-generated B cells, as an outcome of B-1 cell development, can progress to become lymphocytosis, lymphoma, and MCL-like neoplasia in aged mice.

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Section: Introductionmentioning

confidence: 99%

Early Generated B-1–Derived B Cells Have the Capacity To Progress To Become Mantle Cell Lymphoma–like Neoplasia in Aged Mice

Hayakawa

Formica

Nakao

et al. 2018

The Journal of Immunology

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“…Two models have been proposed to explain adult peritoneal B-1 cell origin: (i) a B-cell 80 3 0 0 3 M581 58 14 2 7 5 M582 88 13 2 9 2 M584 70 5 0 5 0 M585 73 15 2 7 6 S253 58 8 4 3 1 S259 55 5 2 3 0 T262 79 4 3 0 1 T263 70 6 0 0 6 T269 69 8 4 0 4 T270 66 5 (55,56) or by genetic manipulation (43,57,58) has not been discarded. However, it is now evident that B-1P are generated in adult bone marrow (38,39,42).…”

Section: Discussionmentioning

confidence: 99%

“…B-1a cells are more efficiently produced by fetal (and neonatal) than by adult progenitors (42,55,56,61). B-1a is also the main B-1 subtype generated when adult cells are reprogrammed by Lin28b transduction (58,59). In contrast, adult B-1P give rise preferentially, but not exclusively, to B-1b cells (38)(39)(40)55).…”

Section: Discussionmentioning

confidence: 99%

Role of Polycomb RYBP in Maintaining the B-1-to-B-2 B-Cell Lineage Switch in Adult Hematopoiesis

Calés

Pavón

Starowicz

et al. 2016

Molecular and Cellular Biology

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dPolycomb chromatin modifiers regulate hematopoietic pluripotent stem and progenitor cell self-renewal and expansion. Polycomb complex redundancy and biochemical heterogeneity complicate the unraveling of the functional contributions of distinct components. We have studied the hematopoietic activity of RYBP, a direct interactor and proposed modulator of RING1A/ RING1B-dependent histone H2A monoubiquitylation (H2AUb). Using a mouse model to conditionally inactivate Rybp in adult hematopoiesis, we have found that RYBP deletion results in a reversion of B-1-to-B-2 B-cell progenitor ratios, i.e., of the innate (predominantly fetal) to acquired (mostly adult) immunity precursors. Increased numbers of B-1 progenitors correlated with a loss of pre-proB cells, the B-2 progenitors. RYBP-deficient stem and progenitor cell populations (LKS) and isolated common lymphoid progenitors (CLP) gave rise to increased numbers of B-1 progenitors in vitro. Rybp inactivation, however, did not result in changes of global H2AUb and did not interact genetically with Ring1A or Ring1B deletions. These results show that a sustained regulation of the B-1-to-B-2 switch is needed throughout adult life and that RYBP plays an important role in keeping B-2 dominance, most likely independently of its Polycomb affiliation. RING1 and YY1 binding protein (RYBP) is a component of a subset of type I Polycomb repressive complexes (PRC1), chromatin regulators endowed with histone H2A monoubiquitylating activity (recently reviewed in references 1 and 2). RYBP contacts the C-terminal region of RING1B and its paralog, RING1A (3), heterodimeric RING-type E3 ubiquitin ligases that modify lysine 119 of histone H2A (H2AUb) (4, 5). Canonical PRC1 assemblies are characterized by the presence of both chromobox-containing subunits and oligomerizing SAM motif subunits, PHC proteins (6, 7). Noncanonical PRC1 complexes, on the other hand, contain RYBP or its paralog, YY1-associated factor (YAF1), instead of chromobox proteins (6, 7), as their association with RING1 proteins is mutually exclusive (8). PRC1 association with chromatin not only modifies H2A but also promotes compaction, a structural alteration that usually correlates with transcriptionally repressed states (6, 9-11). PRC1 is recruited to chromatin through PRC2-induced H3K27me3-dependent and -independent mechanisms (6,7,12). In vitro, RYBP-PRC1 is more efficient at histone monoubiquitylation than canonical PRC1 complexes (6), an observation consistent with in vivo evidence showing decreased levels of global H2AUb upon short-hairpin downregulation of RYBP (6, 7, 13). However, the relative contributions to the H2A modification of RYBP-or chromobox-containing PRC1 complexes still are controversial (6,14), possibly because of cell type variations.In the mouse, genetic analysis of PRC1 functions in differentiation often has focused on the hematopoietic compartment (summarized in references 15 and 16) as one of the best known hierarchies of related cell lineages (17). Most defects in PRC1 mutant lines pertain to...

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“…p50, Malt1, Carma1, Ikk complex), downstream of the BCR, have been shown to be essential for B1 cell development (6). The RNA-binding protein Lin28b, and its downstream effectors Let-7 and Arid3a, were revealed to promote fetal B1 cell lymphopoiesis (7,8). Similarly, Ebf1 is required, and its overexpression induces B1 cell development at the expense of B2 cells (9,10).…”

Section: Cd19mentioning

confidence: 99%

Ikaros Is a Negative Regulator of B1 Cell Development and Function

Macias-Garcia

Heizmann

Sellars

et al. 2016

Journal of Biological Chemistry

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B1 B cells secrete most of the circulating natural antibodies and are considered key effector cells of the innate immune response. However, B1 cell-associated antibodies often crossreact with self-antigens, which leads to autoimmunity, and B1 cells have been implicated in cancer. How B1 cell activity is regulated remains unclear. We show that the Ikaros transcription factor is a major negative regulator of B1 cell development and function. Using conditional knock-out mouse models to delete Ikaros at different locations, we show that Ikaros-deficient mice exhibit specific and significant increases in splenic and bone marrow B1 cell numbers, and that the B1 progenitor cell pool is increased ϳ10-fold in the bone marrow. Ikaros-null B1 cells resemble WT B1 cells at the molecular and cellular levels, but show a down-regulation of signaling components important for inhibiting proliferation and immunoglobulin production. Ikarosnull B1 cells hyper-react to TLR4 stimulation and secrete high amounts of IgM autoantibodies. These results indicate that Ikaros is required to limit B1 cell homeostasis in the adult.

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Lin28b promotes fetal B lymphopoiesis through the transcription factor Arid3a

Cited by 114 publications

References 34 publications

Early Generated B-1–Derived B Cells Have the Capacity To Progress To Become Mantle Cell Lymphoma–like Neoplasia in Aged Mice

Early Generated B-1–Derived B Cells Have the Capacity To Progress To Become Mantle Cell Lymphoma–like Neoplasia in Aged Mice

Role of Polycomb RYBP in Maintaining the B-1-to-B-2 B-Cell Lineage Switch in Adult Hematopoiesis

Ikaros Is a Negative Regulator of B1 Cell Development and Function

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