Zhaoqing Ba
Tsinghua University
Molecular biologyV(D)J recombinationDNAChromatinBiology
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Publications 13
#1Huan Chen (Harvard University)H-Index: 1
#2Yuxiang Zhang (Harvard University)H-Index: 13
Last. Donna Neuberg (Harvard University)H-Index: 115
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The antigen-binding variable regions of the B cell receptor (BCR) and of antibodies are encoded by exons that are assembled in developing B cells by V(D)J recombination1. The BCR repertoires of primary B cells are vast owing to mechanisms that create diversity at the junctions of V(D)J gene segments that contribute to complementarity-determining region 3 (CDR3), the region that binds antigen1. Primary B cells undergo antigen-driven BCR affinity maturation through somatic hypermutation and cellul...
1 CitationsSource
#1Zhaoqing Ba (HHMI: Howard Hughes Medical Institute)H-Index: 4
#2Jiangman Lou (HHMI: Howard Hughes Medical Institute)
Last. Frederick W. Alt (HHMI: Howard Hughes Medical Institute)H-Index: 157
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RAG endonuclease initiates V(D)J recombination in progenitor (pro)-B cells1. Upon binding a recombination center (RC)-based JH, RAG scans upstream chromatin via loop extrusion, potentially mediated by cohesin2-10, to locate Ds and assemble a DJH-based RC11. CTCF looping factor-bound elements (CBEs) within IGCR1 upstream of Ds impede RAG-scanning12-15; but their inactivation allows scanning to proximal VHs where additional CBEs activate rearrangement and impede scanning any further upstream15,16....
#1Xuefei Zhang (Harvard University)H-Index: 2
#2Yu ZhangH-Index: 12
Last. Frederick W. Alt (Harvard University)H-Index: 157
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Antibody class switch recombination (CSR) in B lymphocytes replaces immunoglobulin heavy chain locus (Igh) Cμ constant region exons (CHs) with one of six CHs lying 100–200 kb downstream1. Each CH is flanked upstream by an I promoter and long repetitive switch (S) region1. Cytokines and activators induce activation-induced cytidine deaminase (AID)2 and I-promoter transcription, with 3′ IgH regulatory region (3′ IgHRR) enhancers controlling the latter via I-promoter competition for long-range 3′ I...
4 CitationsSource
#1Yu ZhangH-Index: 12
#1Yu ZhangH-Index: 45
Last. Frederick W. Alt (Harvard University)H-Index: 157
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The RAG endonuclease initiates Igh V(D)J assembly in B cell progenitors by joining D segments to JH segments, before joining upstream VH segments to DJH intermediates1. In mouse progenitor B cells, the CTCF-binding element (CBE)-anchored chromatin loop domain2 at the 3′ end of Igh contains an internal subdomain that spans the 5′ CBE anchor (IGCR1)3, the DH segments, and a RAG-bound recombination centre (RC)4. The RC comprises the JH-proximal D segment (DQ52), four JH segments, and the intronic e...
9 CitationsSource
#1Suvi Jain (Boston Children's Hospital)H-Index: 3
#2Zhaoqing Ba (Boston Children's Hospital)H-Index: 4
Last. Frederick W. Alt (Boston Children's Hospital)H-Index: 157
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Summary RAG endonuclease initiates antibody heavy chain variable region exon assembly from V, D, and J segments within a chromosomal V(D)J recombination center (RC) by cleaving between paired gene segments and flanking recombination signal sequences (RSSs). The IGCR1 control region promotes DJ H intermediate formation by isolating Ds, J H s, and RCs from upstream V H s in a chromatin loop anchored by CTCF-binding elements (CBEs). How V H s access the DJ H RC for V H to DJ H rearrangement was unk...
20 CitationsSource
#1Sherry G. Lin (HHMI: Howard Hughes Medical Institute)H-Index: 2
#2Zhaoqing Ba (HHMI: Howard Hughes Medical Institute)H-Index: 4
Last. Yu Zhang (HHMI: Howard Hughes Medical Institute)H-Index: 45
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Abstract An effective adaptive immune system depends on the ability of developing B and T cells to generate diverse immunoglobulin (Ig) and T cell receptor repertoires, respectively. Such diversity is achieved through a programmed somatic recombination process whereby germline V, D, and J segments of antigen receptor loci are assembled to form the variable region V(D)J exons of Ig and TCRs. Studies of this process, termed V(D)J recombination, have provided key insights into our understanding of ...
2 CitationsSource
#1Mingming Liu (PKU: Peking University)H-Index: 1
#2Zhaoqing Ba (THU: Tsinghua University)H-Index: 4
Last. Yijun Qi (THU: Tsinghua University)H-Index: 42
view all 10 authors...
Repair of DNA double-strand breaks (DSBs) is critical for the maintenance of genome integrity. We previously showed that DSB-induced small RNAs (diRNAs) facilitate homologous recombination (HR)-mediated DSB repair in Arabidopsis thaliana. Here we show that INVOLVED IN DE NOVO 2 (IDN2), a double-stranded RNA (dsRNA) binding protein involved in small RNA-directed DNA methylation, is required for DSB repair in Arabidopsis. We find that IDN2 interacts with the heterotrimeric replication protein A (R...
4 CitationsSource
#1Zhaoqing Ba (HHMI: Howard Hughes Medical Institute)H-Index: 4
#2Jiazhi Hu (HHMI: Howard Hughes Medical Institute)H-Index: 12
Last. Frederick W. Alt (HHMI: Howard Hughes Medical Institute)H-Index: 157
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The N-terminal variable regions of immunoglobulin (Ig) heavy (IgH) and light (IgL) chains are involved in specific antigen binding and assembled from germline variable (V), diversity (D), and joining (J) gene segments through a somatic recombination reaction known as V(D)J recombination. V(D)J recombination is initiated by RAG endonuclease and completed by non-homologous DNA end-joining. V(D)J recombination is tightly regulated in the contexts of order, lineage, and allelic exclusion. For IgL th...
#1Sherry G. Lin (Harvard University)H-Index: 2
#2Zhaoqing Ba (Harvard University)H-Index: 4
Last. Frederick W. Alt (Harvard University)H-Index: 157
view all 6 authors...
Developing B lymphocytes undergo V(D)J recombination to assemble germ-line V, D, and J gene segments into exons that encode the antigen-binding variable region of Ig heavy (H) and light (L) chains. IgH and IgL chains associate to form the B-cell receptor (BCR), which, upon antigen binding, activates B cells to secrete BCR as an antibody. Each of the huge number of clonally independent B cells expresses a unique set of IgH and IgL variable regions. The ability of V(D)J recombination to generate v...
20 CitationsSource
#1Zhaoqing Ba (HHMI: Howard Hughes Medical Institute)H-Index: 4
#2Fei-Long Meng (HHMI: Howard Hughes Medical Institute)H-Index: 14
Last. Frederick W. Alt (HHMI: Howard Hughes Medical Institute)H-Index: 157
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The Epstein–Barr virus (EBV) latent membrane protein 1 (LMP1) contributes to oncogenic human B-cell transformation. Mouse B cells conditionally expressing LMP1 are not predisposed to B-cell malignancies, as LMP1-expressing B cells are eliminated by T cells. However, mice with conditional B-cell LMP1 expression and genetic elimination of α/β and γ/δ T cells (“CLT” mice) die early in association with B-cell lymphoproliferation and lymphomagenesis. Generation of CLT mice involves in-breeding multip...
2 CitationsSource