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BRWD1 orchestrates small pre-B cell chromatin topology by converting static to dynamic cohesin

Mandal and colleagues report how the chromatin modulator BRWD1 mediates extensive changes in 3D chromatin topology during B cell development by converting static to dynamic cohesin.

Malay Mandal
Mark Maienschein-Cline
Marcus R. Clark
Research20 Nov 2023
Nature Immunology

Volume: 25, P: 129-141
CXCR4 signaling directs Igk recombination and the molecular mechanisms of late B lymphopoiesis

Pre-B cells undergo a transition checkpoint needed for developmental progression. Mandal and colleagues show that the CXCL12–CXCR4 signaling axis orchestrates late B cell lymphopoiesis by suppressing Myc and cyclin D genes and promoting Rag-mediated recombination of immunoglobulin light-chain genes.

Malay Mandal
Michael K. Okoreeh
Marcus R. Clark
Research02 Sept 2019
Nature Immunology

Volume: 20, P: 1393-1403
Publisher Correction: A shared Runx1-bound Zbtb16 enhancer directs innate and innate-like lymphoid lineage development

Ai-Ping Mao
Isabel E. Ishizuka
Albert Bendelac
Amendments and CorrectionsOpen Access30 Nov 2017
Nature Communications

Volume: 8, P: 1
B-1a cells acquire their unique characteristics by bypassing the pre-BCR selection stage

B-1a B cells are innate-like cells with biased reactivity to bacteria and self-antigens. Here the authors show that reduced interleukin-7 in developing fetal liver-derived pro-B cells induces premature immunoglobulin κ rearrangement, alleviating the requirement for a pre-BCR selection stage and allowing the generation of autoreactive B1-a B cells.

Jason B. Wong
Susannah L. Hewitt
Jane A. Skok
ResearchOpen Access18 Oct 2019
Nature Communications

Volume: 10, P: 1-15
Novel specialized cell state and spatial compartments within the germinal center

Germinal centers are typically divided into dark and light zones. Clark and colleagues identify ‘gray zone’ cyclin B1⁺ B cell clusters as sites of ongoing cell proliferation, and these cells are distinct from dark zone B cells that undergo AID-dependent somatic hypermutation. This separation of function safeguards B cells undergoing DNA replication against potential mutagenic events that could result in neoplastic transformation.

Domenick E. Kennedy
Michael K. Okoreeh
Marcus R. Clark
Research27 Apr 2020
Nature Immunology

Volume: 21, P: 660-670
A shared Runx1-bound Zbtb16 enhancer directs innate and innate-like lymphoid lineage development

Zbtb16-encoded transcription factor PLZF directs the differentiation of multiple innate and innate-like cell lineages, but how Zbtb16 itself is regulated remains unclear. Here the authors show, using CRISPR gene editing, ATAC-seq and ChIP-seq, that specific Runx1-bound enhancer elements critically modulate lineage-dependent expressions of PLZF.

Ai-Ping Mao
Isabel E. Ishizuka
Albert Bendelac
ResearchOpen Access16 Oct 2017
Nature Communications

Volume: 8, P: 1-14
Ras orchestrates exit from the cell cycle and light-chain recombination during early B cell development

How signals through the pre–B cell antigen receptor (pre-BCR) and IL-7 receptor (IL-7R) coordinate population expansion of pre-B cells with subsequent recombination of the immunoglobulin κ-chain locus is unclear. Clark and colleagues show that pre-BCR signaling via the Ras-MEK-Erk pathway poises pre–B cells to undergo differentiation after escaping IL-7R signaling.

Malay Mandal
Sarah E Powers
Marcus R Clark
Research06 Sept 2009
Nature Immunology

Volume: 10, P: 1110-1117
Hedgehog signaling controls thymocyte progenitor homeostasis and differentiation in the thymus

Abdeljabar El Andaloussi
Stephanie Graves
Iannis Aifantis
Research05 Mar 2006
Nature Immunology

Volume: 7, P: 418-426
Targeting the NF-κB signaling pathway in Notch1-induced T-cell leukemia

Tomas Vilimas
Joaquina Mascarenhas
Iannis Aifantis
Research17 Dec 2006
Nature Medicine

Volume: 13, P: 70-77
BRWD1 orchestrates epigenetic landscape of late B lymphopoiesis

B-cell development is tightly regulated by transcription programs that are coordinated by transcription factors (TF) and locus accessibility. Here the authors show that, in mice and humans, the epigenetic reader BRWD1 inhibits and promotes the accessibility of enhancers for early and late B lymphopoiesis, respectively.

Malay Mandal
Mark Maienschein-Cline
Marcus R. Clark
ResearchOpen Access24 Sept 2018
Nature Communications

Volume: 9, P: 1-15
Histone reader BRWD1 targets and restricts recombination to the Igk locus

V(D)J recombination is developmentally regulated and occurs at restricted sites within the genome. Clark and colleagues show that the histone reader BRWD1 is required for precise positioning of nucleosomes and targeting of RAG recombinase proteins within the Igk locus.

Malay Mandal
Keith M Hamel
Marcus R Clark
Research24 Aug 2015
Nature Immunology

Volume: 16, P: 1094-1103
Epigenetic repression of the Igk locus by STAT5-mediated recruitment of the histone methyltransferase Ezh2

The transcription factor STAT5 commonly activates gene transcription. Clark and colleagues show that tetrameric STAT5, induced by high concentrations of interleukin 7, can repress gene expression by recruitment of the histone methyltransferase Ezh2.

Malay Mandal
Sarah E Powers
Marcus R Clark
Research30 Oct 2011
Nature Immunology

Volume: 12, P: 1212-1220
A self-reinforcing regulatory network triggered by limiting IL-7 activates pre-BCR signaling and differentiation

Cycling and cell cycle–arrested pre-B cells both express pre-BCRs, but whether qualitative differences exist in downstream signaling pathways remains controversial. Singh and colleagues show that differences in expression of the adaptor BLNK underlie functional distinctions in pre-BCR signaling.

Kyoko Ochiai
Mark Maienschein-Cline
Harinder Singh
Research22 Jan 2012
Nature Immunology

Volume: 13, P: 300-307
Relationships between physical properties and sequence in silkworm silks

Ali D. Malay
Ryota Sato
Keiji Numata
ResearchOpen Access09 Jun 2016
Scientific Reports

Volume: 6, P: 1-11
Orchestrating B cell lymphopoiesis through interplay of IL-7 receptor and pre-B cell receptor signalling

Developing B cells that have successfully expressed a pre-B cell receptor (pre-BCR) undergo clonal expansion, but must exit the cell cycle before rearranging their immunoglobulin light chain loci. The authors discuss how signalling through the interleukin-7 receptor and BCR is coordinated in a mutually exclusive manner to ensure the production of mature B cells without risking leukaemic transformation.

Marcus R. Clark
Malay Mandal
Harinder Singh
Reviews31 Dec 2013
Nature Reviews Immunology

Volume: 14, P: 69-80

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BRWD1 orchestrates small pre-B cell chromatin topology by converting static to dynamic cohesin

CXCR4 signaling directs Igk recombination and the molecular mechanisms of late B lymphopoiesis

Publisher Correction: A shared Runx1-bound Zbtb16 enhancer directs innate and innate-like lymphoid lineage development

B-1a cells acquire their unique characteristics by bypassing the pre-BCR selection stage

Novel specialized cell state and spatial compartments within the germinal center

A shared Runx1-bound Zbtb16 enhancer directs innate and innate-like lymphoid lineage development

Ras orchestrates exit from the cell cycle and light-chain recombination during early B cell development

Hedgehog signaling controls thymocyte progenitor homeostasis and differentiation in the thymus

Targeting the NF-κB signaling pathway in Notch1-induced T-cell leukemia

BRWD1 orchestrates epigenetic landscape of late B lymphopoiesis

Histone reader BRWD1 targets and restricts recombination to the Igk locus

Epigenetic repression of the Igk locus by STAT5-mediated recruitment of the histone methyltransferase Ezh2

A self-reinforcing regulatory network triggered by limiting IL-7 activates pre-BCR signaling and differentiation

Relationships between physical properties and sequence in silkworm silks

Orchestrating B cell lymphopoiesis through interplay of IL-7 receptor and pre-B cell receptor signalling

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