Bibliographic Details
Title: |
Maf expression in B cells restricts reactive plasmablast and germinal center B cell expansion. |
Authors: |
Hillion, Sophie, Miranda, Anjelica, Le Dantec, Christelle, Boudigou, Marina, Le Pottier, Laƫtitia, Cornec, Divi, Torres, Raul M., Pelanda, Roberta |
Source: |
Nature Communications; 9/12/2024, Vol. 15 Issue 1, p1-16, 16p |
Subject Terms: |
B cell differentiation, PLASMA cells, B cells, TRANSCRIPTION factors, IMMUNOLOGIC memory |
Abstract: |
Precise regulation of B cell differentiation is essential for an effective adaptive immune response. Here, we show that B cell development in mice with B cell-specific Maf deletion is unaffected, but marginal zone B cells, germinal centre B cells, and plasmablasts are significantly more frequent in the spleen of naive Maf-deficient mice compared to wild type controls. In the context of a T cell-dependent immunization, Maf deletion causes increased proliferation of germinal centre B cells and extrafollicular plasmablasts. This is accompanied by higher production of antigen-specific IgG1 antibodies with minimal modification of early memory B cells, but a reduction in plasma cell numbers. Single-cell RNA sequencing shows upregulation of genes associated with DNA replication and cell cycle progression, confirming the role of Maf in cell proliferation. Subsequent pathway analysis reveals that Maf influences cellular metabolism, transporter activity, and mitochondrial proteins, which have been implicated in controlling the germinal centre reaction. In summary, our findings demonstrate that Maf acts intrinsically in B cells as a negative regulator of late B cell differentiation, plasmablast proliferation and germinal centre B cell formation. Maf is a transcription factor regulating pivotal biological processes in multiple immune cells, but its B-cell-intrinsic role is not fully known. Here authors show that genomic deletion of Maf in the B cell lineage does not disturb the sequence of developmental stages, however, removes an important inhibitory step to restrict the early steps of germinal centre B cell and extrafollicular plasmablast population expansion. [ABSTRACT FROM AUTHOR] |
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Database: |
Complementary Index |