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Activation and accumulation of B cells in TACI-deficient mice

Abstract

The tumor necrosis factor (TNF)-related ligand B lymphocyte stimulator (BLyS) binds two TNF receptor family members, transmembrane activator and calcium-modulating and cyclophilin ligand interactor (TACI) and B cell maturation molecule (BCMA). Mice that are transgenic for BLyS show B cell accumulation, activation and autoimmune lupus-like nephritis. The existence of at least two distinct BLyS receptors raises the question of the relative contribution of each to B cell functions. We therefore generated mice that were deficient in TACI. TACI−/− mice showed increased B cell accumulation and marked splenomegaly. Isolated TACI−/− B cells hyperproliferated and produced increased amounts of immunoglobulins in vitro. In vivo antigen challenge resulted in enhanced antigen-specific antibody production. Thus, TACI may play an unexpected inhibitory role in B cell activation that helps maintain immunological homeostasis.

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Figure 1: Targeting of Taci by homologous recombination.
Figure 2: Altered splenic architecture in TACI-deficient mice with prominent white pulp and increased cellularity of B cells follicles.
Figure 3: Well developed germinal centers in the spleen of TACI−/− mice.
Figure 4: B cells from TACI−/− mice hyperproliferate in vitro.
Figure 5: B cells lacking TACI produce higher amounts of immunoglobulins upon in vitro stimulation.
Figure 6: Humoral responses to TD and TI antigens in TACI−/− mice.

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Acknowledgements

We thank B. Wright for help with immunohistochemistry and S. Schilbach for DNA sequencing.

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Correspondence to Iqbal S. Grewal or Vishva M. Dixit.

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Yan, M., Wang, H., Chan, B. et al. Activation and accumulation of B cells in TACI-deficient mice. Nat Immunol 2, 638–643 (2001). https://doi.org/10.1038/89790

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