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1.
EMBO Rep ; 24(8): e56420, 2023 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-37424400

RESUMO

Chronic Lymphocytic Leukemia (CLL) is the most common leukemia in adults in the Western world. B cell receptor (BCR) signaling is known to be crucial for the pathogenesis and maintenance of CLL cells which develop from mature CD5+ B cells. BCR signaling is regulated by the inhibitory co-receptor Siglec-G and Siglec-G-deficient mice have an enlarged CD5+ B1a cell population. Here, we determine how Siglec-G expression influences the severity of CLL. Our results show that Siglec-G deficiency leads to earlier onset and more severe course of the CLL-like disease in the murine Eµ-TCL1 model. In contrast, mice overexpressing Siglec-G on the B cell surface are almost completely protected from developing CLL-like disease. Furthermore, we observe a downmodulation of the human ortholog Siglec-10 from the surface of human CLL cells. These results demonstrate a critical role for Siglec-G in disease progression in mice, and suggest that a similar mechanism for Siglec-10 in human CLL may exist.


Assuntos
Leucemia Linfocítica Crônica de Células B , Camundongos , Animais , Humanos , Leucemia Linfocítica Crônica de Células B/genética , Leucemia Linfocítica Crônica de Células B/metabolismo , Leucemia Linfocítica Crônica de Células B/patologia , Lectinas Semelhantes a Imunoglobulina de Ligação ao Ácido Siálico/genética , Camundongos Transgênicos , Proteínas Proto-Oncogênicas , Linfócitos B/metabolismo , Receptores de Antígenos de Linfócitos B/genética
2.
PLoS Pathog ; 16(4): e1008464, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32324805

RESUMO

Streptococcus pneumoniae is a major human pathogen, causing pneumonia and sepsis. Genetic components strongly influence host responses to pneumococcal infections, but the responsible loci are unknown. We have previously identified a locus on mouse chromosome 7 from a susceptible mouse strain, CBA/Ca, to be crucial for pneumococcal infection. Here we identify a responsible gene, Cd22, which carries a point mutation in the CBA/Ca strain, leading to loss of CD22 on B cells. CBA/Ca mice and gene-targeted CD22-deficient mice on a C57BL/6 background are both similarly susceptible to pneumococcal infection, as shown by bacterial replication in the lungs, high bacteremia and early death. After bacterial infections, CD22-deficient mice had strongly reduced B cell populations in the lung, including GM-CSF producing, IgM secreting innate response activator B cells, which are crucial for protection. This study provides striking evidence that CD22 is crucial for protection during invasive pneumococcal disease.


Assuntos
Linfócitos B/imunologia , Infecções Pneumocócicas/imunologia , Lectina 2 Semelhante a Ig de Ligação ao Ácido Siálico/imunologia , Animais , Linfócitos B/microbiologia , Bacteriemia/genética , Bacteriemia/imunologia , Bacteriemia/microbiologia , Feminino , Interações Hospedeiro-Patógeno , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos CBA , Infecções Pneumocócicas/genética , Infecções Pneumocócicas/metabolismo , Pneumonia Pneumocócica/genética , Pneumonia Pneumocócica/imunologia , Pneumonia Pneumocócica/metabolismo , Pneumonia Pneumocócica/microbiologia , Lectina 2 Semelhante a Ig de Ligação ao Ácido Siálico/deficiência , Lectina 2 Semelhante a Ig de Ligação ao Ácido Siálico/genética , Streptococcus pneumoniae/patogenicidade
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