TSC1 Promotes B Cell Maturation but Is Dispensable for Germinal Center Formation.
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Accumulating evidence indicates that the tuberous sclerosis complex 1 (TSC1), a tumor suppressor that acts by inhibiting mTOR signaling, plays an important role in the immune system. We report here that TSC1 differentially regulates mTOR complex 1 (mTORC1) and mTORC2/Akt signaling in B cells. TSC1 deficiency results in the accumulation of transitional-1 (T1) B cells and progressive losses of B cells as they mature beyond the T1 stage. Moreover, TSC1KO mice exhibit a mild defect in the serum antibody responses or rate of Ig class-switch recombination after immunization with a T-cell-dependent antigen. In contrast to a previous report, we demonstrate that both constitutive Peyer's patch germinal centers (GCs) and immunization-induced splenic GCs are unimpaired in TSC1-deficient (TSC1KO) mice and that the ratio of GC B cells to total B cells is comparable in WT and TSC1KO mice. Together, our data demonstrate that TSC1 plays important roles for B cell development, but it is dispensable for GC formation and serum antibody responses.
Proto-Oncogene Proteins c-akt
TOR Serine-Threonine Kinases
Tumor Suppressor Proteins
Published Version (Please cite this version)10.1371/journal.pone.0127527
Publication InfoCarico, Z; Ci, X; Deng, X; Hopper, K; Kelsoe, Garnett; Kuraoka, M; ... Zhong, XP (2015). TSC1 Promotes B Cell Maturation but Is Dispensable for Germinal Center Formation. PLoS One, 10(5). pp. e0127527. 10.1371/journal.pone.0127527. Retrieved from http://hdl.handle.net/10161/10894.
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Research Assistant, Ph D Student
James B. Duke Professor of Immunology
1. Lymphocyte development and antigen-driven diversification of immunoglobulin and T cell antigen receptor genes. 2. The germinal center reaction and mechanisms for clonal selection and self - tolerance. The origins of autoimmunity. 3. Interaction of innate- and adaptive immunity and the role of inflammation in lymphoid organogenesis. 4. The role of secondary V(D)J gene rearrangment in lymphocyte development and malignancies. 5. Mathematical modeling of immune responses,
Assistant Research Professor of Immunology
Garnett Kelsoe Laboratory
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