TSC1 Promotes B Cell Maturation but Is Dispensable for Germinal Center Formation.

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Date

2015

Authors

Ci, Xinxin
Kuraoka, Masayuki
Wang, Hongxia
Carico, Zachary
Hopper, Kristen
Shin, Jinwook
Deng, Xuming
Qiu, Yirong
Unniraman, Shyam
Kelsoe, Garnett

Editors

Lu, Shan

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Abstract

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.

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Published Version (Please cite this version)

10.1371/journal.pone.0127527

Publication Info

Ci, Xinxin, Masayuki Kuraoka, Hongxia Wang, Zachary Carico, Kristen Hopper, Jinwook Shin, Xuming Deng, Yirong Qiu, et al. (2015). TSC1 Promotes B Cell Maturation but Is Dispensable for Germinal Center Formation. PLoS One, 10(5). p. e0127527. 10.1371/journal.pone.0127527 Retrieved from https://hdl.handle.net/10161/10894.

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Scholars@Duke

Kelsoe

Garnett H. Kelsoe

James B. Duke Distinguished 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, DNA motifs, collaborations in bioinformatics.
    6. Humoral immunity to influenza and HIV-1.
Zhong

Xiaoping Zhong

Professor of Pediatrics

The immune system protects the host from microbial infection but can cause diseases if not properly controlled. My lab is interested in the receptor signaling mediated regulation of immune cell development and function as well as the pathogenesis and treatment of autoimmune diseases and allergies.

We are currently investigating the roles diacylglycerol kinases (DGKs) and TSC1/2-mTOR play in the immune system. DGKs are a family of ten enzymes that catalyze the conversion of diacylglycerol (DAG) to phosphatidic acid (PA), Both DAG and PA are important second messengers involved signaling from numerous receptors. While we expect DGKs to perform important roles in development and cellular function by modulating DAG and PA levels, the physiologic functions of DGKs have been poorly understood. Using cell line models and genetically manipulated mice, we have demonstrated that DGKα and ζ isoforms play critical roles in: T cell development, activation, and anergy by regulating T cell receptor signaling; FcεRI signaling and mast cell function; and Toll-like receptor signaling and innate immune responses.

Research areas that we are actively pursuing include:
1. The mechanisms that control T cell maturation, activation
and self-tolerance.
2. NKT cell development and function.
3. Thymic epithelial cells and thymic development, function, and involution.
4. Regulation of Toll-like receptor signaling and innate immunity. 
5. The pathogenesis and treatment of autoimmune hepatitis. 
6. Mast cell development and function.
7. The pathogenesis and immunotherapy for peanut allergy.


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