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Attenuation of Apoptosis Underlies B Lymphocyte Stimulator Enhancement of Humoral Immune Response
| Content Provider | Scilit |
|---|---|
| Author | Do, Richard Hatada, Eunice Lee, Hayyoung Tourigny, Michelle R. Hilbert, David Chen-Kiang, Selina |
| Copyright Year | 2000 |
| Description | B lymphocyte stimulator (BLyS) is a newly identified monocyte-specific TNF family cytokine. It has been implicated in the development of autoimmunity, and functions as a potent costimulator with antiimmunoglobulin M in B cell proliferation in vitro. Here we demonstrate that BLyS prominently enhances the humoral responses to both T cell–independent and T cell–dependent antigens, primarily by attenuation of apoptosis as evidenced by the prolonged survival of antigen-activated B cells in vivo and in vitro. BLyS acts on primary splenic B cells autonomously, and directly cooperates with CD40 ligand (CD40L) in B cell activation in vitro by protecting replicating B cells from apoptosis. Moreover, although BLyS alone cannot activate the cell cycle, it is sufficient to prolong the survival of naive resting B cells in vitro. Attenuation of apoptosis by BLyS correlates with changes in the ratios between Bcl-2 family proteins in favor of cell survival, predominantly by reducing the proapoptotic Bak and increasing its prosurvival partners, Bcl-2 and Bcl-xL. In either resting or CD40L-activated B cells, the NF-κB transcription factors RelB and p50 are specifically activated, suggesting that they may mediate BLyS signals for B cell survival. Together, these results provide direct evidence for BLyS enhancement of both T cell–independent and T cell–dependent humoral immune responses, and imply a role for BLyS in the conservation of the B cell repertoire. The ability of BLyS to increase B cell survival indiscriminately, at either a resting or activated state, and to cooperate with CD40L, further suggests that attenuation of apoptosis underlies BLyS enhancement of polyclonal autoimmunity as well as the physiologic humoral immune response. |
| Related Links | http://jem.rupress.org/content/192/7/953.full.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193312/pdf https://rupress.org/jem/article-pdf/192/7/953/980496/000917.pdf |
| Ending Page | 964 |
| Page Count | 12 |
| Starting Page | 953 |
| DOI | 10.1084/jem.192.7.953 |
| Journal | The Journal of experimental medicine |
| Issue Number | 7 |
| Volume Number | 192 |
| Language | English |
| Publisher | Rockefeller University Press |
| Publisher Date | 2000-10-02 |
| Access Restriction | Open |
| Subject Keyword | Immunology Primary B Cell Cd40 Nuclear Factor Κb Bcl-2 Autoimmunity Journal: The Journal of experimental medicine (Vol- 192, Issue- 7) |
| Content Type | Text |
