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

PLoS One. 2015 May 22;10(5):e0127527. doi: 10.1371/journal.pone.0127527. eCollection 2015.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity / immunology
  • Animals
  • Antibody Formation / immunology
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism*
  • Germinal Center / immunology
  • Germinal Center / metabolism*
  • Lymphocyte Activation / immunology
  • Mechanistic Target of Rapamycin Complex 1
  • Mechanistic Target of Rapamycin Complex 2
  • Mice
  • Mice, Knockout
  • Multiprotein Complexes / metabolism
  • Peyer's Patches / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction / immunology*
  • Spleen / immunology
  • Spleen / metabolism*
  • TOR Serine-Threonine Kinases / metabolism
  • Tuberous Sclerosis Complex 1 Protein
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism*

Substances

  • Multiprotein Complexes
  • Tsc1 protein, mouse
  • Tuberous Sclerosis Complex 1 Protein
  • Tumor Suppressor Proteins
  • Mechanistic Target of Rapamycin Complex 1
  • Mechanistic Target of Rapamycin Complex 2
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases