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Transcriptional analysis of the B cell germinal center reaction
Open accessAbstract
The germinal center (GC) reaction is crucial for T cell-dependent immune responses and is targeted by B cell lymphomagenesis. Here we analyzed the transcriptional changes that occur in B cells during GC transit (naïve B cells → centroblasts → centrocytes → memory B cells) by gene expression profiling. Naïve B cells, characterized by the expression of cell cycle-inhibitory and antiapoptotic genes, become centroblasts by inducing an atypical proliferation program lacking c-Myc expression, switching to a proapoptotic program, and down-regulating cytokine, chemokine, and adhesion receptors. The transition from GC to memory cells is characterized by a return to a phenotype similar to that of naïve cells except for an apoptotic program primed for both death and survival and for changes in the expression of cell surface receptors including IL-2 receptor β. These results provide insights into the dynamics of the GC reaction and represent the basis for the analysis of B cell malignancies.
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Citations
Cited by
Victora, G. D., & Nussenzweig, M. C. (2012) · Annual Review of Immunology · doi:10.1146/annurev-immunol-020711-075032 · Cited by 1,878
Dynamics of B cells in germinal centres
De Silva, N. S., & Klein, U. (2015) · Nature Reviews Immunology · doi:10.1038/nri3804 · Cited by 1,084
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Chung, W., Eum, H. H., Lee, H.-O., Lee, K.-M., Lee, H.-B., Kim, K.-T., Ryu, H. S., Kim, S., Lee, J. E., Park, Y. H., et al. (2017) · Nature Communications · doi:10.1038/ncomms15081 · Cited by 992
“In the detailed analysis, two subclasses of B lymphocytes were identified, one with an expression signature of centroblasts/centrocytes 38 and the other with that of naive B lymphocytes (Supplementary Fig.”
Alvarez, M. J., Shen, Y., Giorgi, F. M., Lachmann, A., Ding, B. B., Ye, B. H., & Califano, A. (2016) · Nature Genetics · doi:10.1038/ng.3593 · Cited by 966
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“The top component genes significantly enriched in this pathway involve MSH2 and MSH6, which are associated with the transition from naïve B cells to centroblasts (22), and also are required to produce mutations within the immunoglobulin V region during somatic hypermutation (23).”
BackgroundFecteau, J. F., Côté, G., & Néron, S. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.177.6.3728 · Cited by 298
Targeting B cells and plasma cells in autoimmune diseases
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Tuning immune responses: diversity and adaptation of the immunological synapse
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BCL6 represses CHEK1 and suppresses DNA damage pathways in normal and malignant B-cells
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Nishikimi, A., Meller, N., Uekawa, N., Isobe, K.-I., Schwartz, M. A., & Maruyama, M. (2005) · FEBS Letters · doi:10.1016/j.febslet.2005.01.006 · Cited by 70
IFN Regulatory Factor 8 Regulates MDM2 in Germinal Center B Cells
Zhou, J. X., Lee, C. H., Qi, C. F., Wang, H., Naghashfar, Z., Abbasi, S., & Morse, H. C. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0803693 · Cited by 47
Metadata
- Authors
- Klein, U., Tu, Y., Stolovitzky, G. A., Keller, J. L., Haddad, J., Miljkovic, V., Cattoretti, G., Califano, A., & Dalla-Favera, R.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2003-02-25
- Volume
- 100
- Issue
- 5
- Pages
- 2639-2644
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2172230584
- Cited by
- 409
- References
- 0
- FWCI
- 7.38
- Type
- journal article
- Language
- en
- Open access
- green
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