FHL2 Is Essential for Spleen T Cell-Dependent B Cell Activation and Antibody Response.
Immunohorizons
; 4(5): 259-273, 2020 05 20.
Article
em En
| MEDLINE
| ID: mdl-32434880
ABSTRACT
Four-and-a-half LIM domain protein 2 (FHL2) is an adaptor molecule regulating various cellular processes, including signal transduction, transcription, and cell survival. Although involved in inflammation and immune responses, its role in the germinal center reaction and B cell maturation remains unknown. We found that FHL2-/- mouse spleens displayed enlarged follicles with more B cells. When a T cell-dependent immune response was elicited using SRBC, FHL2-/- germinal center area was enhanced 2-fold compared with wild type (WT), concomitant with expanded dark zones. Nevertheless, the SRBC-induced rise in spleen IgG1 expression, and plasma IgG1 levels observed in WT were absent in FHL2-/- mice, and circulating plasma cells were also reduced in FHL2-/- This could be explained by deficient upregulation of spleen activation-induced cytidine deaminase mRNA. Interestingly, FHL2-/- B cells successfully underwent class-switch recombination in vitro, and both activation-induced cytidine deaminase induction and IgG1 response to SRBC were equivalent in B cell-deficient µMT mice transplanted with WT or FHL2-/- bone marrow, suggesting that the defects observed in FHL2-/- mice were not B cell intrinsic. However, spleen lysates from FHL2-/- mice revealed a disturbed spleen microenvironment, with reduced CXCL12 and CXCL13 levels compared with WT. Our data suggest that spleen FHL2 expression is essential for a normal germinal center reaction and proper induction of class-switch recombination in response to a T cell-dependent Ag, leading to the emergence of Ab producing plasma cells. This could be due to the regulation of spleen cytokine production by FHL2.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
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Imunoglobulina G
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Linfócitos B
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Linfócitos T
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Centro Germinativo
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Proteínas com Homeodomínio LIM
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Formação de Anticorpos
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Proteínas Musculares
Limite:
Animals
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article