Attenuation of apoptosis underlies B lymphocyte stimulator enhancement of humoral immune response.

TitleAttenuation of apoptosis underlies B lymphocyte stimulator enhancement of humoral immune response.
Publication TypeJournal Article
Year of Publication2000
AuthorsDo RK, Hatada E, Lee H, Tourigny MR, Hilbert D, Chen-Kiang S
JournalJ Exp Med
Date Published2000 Oct 02
Keywords2,4-Dinitrophenol, Animals, Antibodies, Bacterial, Antibody Formation, Apoptosis, B-Cell Activating Factor, B-Lymphocytes, bcl-2 Homologous Antagonist-Killer Protein, bcl-X Protein, CD40 Ligand, Cells, Cultured, Female, gamma-Globulins, Humans, Lymphocyte Activation, Membrane Proteins, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, NF-kappa B, NF-kappa B p50 Subunit, Nitrophenols, Phenylacetates, Pneumococcal Vaccines, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-bcl-2, Serum Albumin, Bovine, T-Lymphocytes, Transcription Factor RelB, Transcription Factors, Tumor Necrosis Factor-alpha

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-kappaB 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.

Alternate JournalJ Exp Med
PubMed ID11015437
PubMed Central IDPMC2193312
Grant ListGM07739 / GM / NIGMS NIH HHS / United States
CA80204 / CA / NCI NIH HHS / United States
AR44580 / AR / NIAMS NIH HHS / United States
Related Lab: 
Related Faculty: 
Selina Chen-Kiang, Ph.D.

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