Developmental pathways for B cell lymphogenesis are sufficiently known only in mice and humans. However, both of these species rearrange immunoglobulin heavy chains (IgH) before light chains (IgL) while IgL precedes IgH rearrangement in swine. We demonstrate here that this reversed order of rearrangements have some concealed consequences: (1) we confirmed that although IgLκ rearrangement is initial, most IgLλ B cells are generated earlier and before IgH rearrangements, while most IgLκ B cells later and after IgH rearrangements, (2) the second IgLκ rearrangement can occur after IgLλ rearrangement, (3) early formed B cells bear only single in-frame IgH rearrangements, (4) many IgLκ B cells carry IgLλ rearrangements that can be productive and occurring on both alleles in one cell, and (5) although VpreB and λ5 genes are present in swine, they are preferentially expressed in non-B cells. In summary, our findings reveal that swine use an alternative B cell developmental pathway as compared to mice and humans.
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http://dx.doi.org/10.1016/j.dci.2020.103751 | DOI Listing |
Pediatr Blood Cancer
January 2025
Departments of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Rearrangements of cytokine receptor-like factor 2 gene (CRLF2) are present in ∼50% of B-lymphoblastic leukemia/lymphoma (B-ALL) with BCR::ABL1-like features. Herein, we report three patients with CRLF2-rearranged mixed phenotype acute leukemia (MPAL). All three cases were B/myeloid MPAL in young patients harboring P2RY8::CRLF2 or IGH::CRLF2 with additional genomic alterations in signaling (JAK and RAS) and cell cycle (CDKN2A/B) pathways, a genomic profile similar to that in BCR::ABL1-like B-ALL.
View Article and Find Full Text PDFMol Cell
January 2025
Drukier Institute for Children's Health, Department of Pediatrics, Weill Cornell Medicine, New York, NY, USA. Electronic address:
The efficacy of antibody responses is inherently linked to paratope diversity, as generated through V(D)J recombination and somatic hypermutation. Despite this, it is unclear how genetic diversification mechanisms evolved alongside codon optimality and affect antibody expression. Here, we analyze germline immunoglobulin (IG) genes, natural V(D)J repertoires, serum IgG, and monoclonal antibody (mAb) expression through the lens of codon optimality.
View Article and Find Full Text PDFHum Pathol
December 2024
Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic address:
Burkitt lymphoma is a mature aggressive B-cell neoplasm with distinctive clinical and morphologic features, a germinal center B-cell immunophenotype, a high proliferation index and MYC rearrangement with an immunoglobulin gene partner. Initially described in equatorial Africa by a surgeon, Denis Burkitt, African (endemic) Burkitt lymphoma was the first neoplasm shown to be associated with a virus, Epstein-Barr virus (EBV), and the first neoplasm shown to be associated with a chromosomal translocation, IGH::MYC. In this article, we provide a brief historical introduction of Burkitt lymphoma, followed by a review of all aspects of this neoplasm including pathogenesis, clinical presentation, morphology, immunophenotype, cytogenetics and molecular findings.
View Article and Find Full Text PDFZhonghua Jie He He Hu Xi Za Zhi
December 2024
Department of Medical Imaging, Zibo Municipal Hospital, Zibo255400, China.
Pulmonary nodular lymphoid hyperplasia (PNLH) is a rare pulmonary lymphoproliferative disease characterized by the absence of specific clinical and imaging features. Consequently, diagnosis relies heavily on postoperative pathological examination, which often leads to preoperative misdiagnosis. Here, we report an atypical case of PNLH in a 57-year-old female patient who was admitted to hospital after a pulmonary nodule was discovered during a routine physical examination two days earlier.
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