| Autor: |
Kagan Ben Tikva, Sharon, Gurwitz, Neta, Sivan, Ehud, Hirsch, Dana, Hezroni-Barvyi, Hadas, Biram, Adi, Moss, Lihee, Wigoda, Noa, Egozi, Adi, Monziani, Alan, Golani, Ofra, Gross, Menachem, Tenenbaum, Ariel, Shulman, Ziv |
| Předmět: |
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| Zdroj: |
Science Immunology; 2024, Vol. 9 Issue 93, p1-15, 15p |
| Abstrakt: |
Antibody affinity maturation occurs in secondary lymphoid organs within germinal centers (GCs). At these sites, B cells mutate their antibody-encoding genes in the dark zone, followed by preferential selection of the high-affinity variants in the light zone by T cells. The strength of the T cell–derived selection signals is proportional to the B cell receptor affinity and to the magnitude of subsequent Myc expression. However, because the lifetime of Myc mRNA and its corresponding protein is very short, it remains unclear how T cells induce sustained Myc levels in positively selected B cells. Here, by direct visualization of mRNA and active transcription sites in situ, we found that an increase in transcriptional bursts promotes Myc expression during B cell positive selection in GCs. Elevated T cell help signals predominantly enhance the percentage of cells expressing Myc in GCs as opposed to augmenting the quantity of Myc transcripts per individual cell. Visualization of transcription start sites in situ revealed that T cell help promotes an increase in the frequency of transcriptional bursts at the Myc locus in GC B cells located primarily in the LZ apical rim. Thus, the rise in Myc, which governs positive selection of B cells in GCs, reflects an integration of transcriptional activity over time rather than an accumulation of transcripts at a specific time point. Editor's summary: After positive selection by T cells in the germinal center (GC) light zone, GC B cells express MYC that activates downstream cell cycle and metabolic gene programs. The half-life of MYC is short, and it is unclear how Myc accumulates in GC B cells to determine their fate. Kagan Ben Tikva et al. used a single-molecule fluorescence in situ hybridization (smFISH) approach to visualize the dynamics of Myc mRNA transcription in murine GC B cells receiving varying degrees of T cell help. T cell–derived signals enhanced the frequency of Myc transcriptional bursts in GC B cells rather than the abundance of transcripts per cell at a single time point, indicating that Myc expression in positively selected B cells is integrated over time. —Hannah Isles [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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