Requirement for Rictor in Homeostasis and Function of Mature B Lymphoid Cells

Blood. 2013 Oct 3;122(14):2369-79. doi: 10.1182/blood-2013-01-477505. Epub 2013 Aug 19.

Abstract

The mammalian target of rapamycin (mTOR), an essential serine/threonine kinase, functions in biochemically distinct multiprotein complexes, but little is known about roles of the complexes in B cells. The acutely rapamycin-sensitive mTOR complex 1 (mTORC1) is defined by a core subunit Raptor, whereas mTORC2 lacks Raptor and, instead, has Rictor and SIN1 as distinct essential components. We now show that homeostasis and function of B cells require Rictor. Conditional deletion of Rictor before lymphoid specification impaired generation of mature follicular, marginal zone, and B1a B lymphocytes. Induced inactivation in adult mice caused cell-autonomous defects in B lymphoid homeostasis and antibody responses in vivo, along with affecting plasma cells in bone marrow. Survival of B lymphocytes depended on Rictor, which was vital for normal induction of prosurvival genes, suppression of proapoptotic genes, nuclear factor κB induction after B-cell receptor stimulation, and B-cell activating factor-induced nuclear factor κB2/p52 generation. Collectively, the findings provide evidence that mTOR signaling affects survival and proliferation of mature B lymphocytes, and establish Rictor as an important signal relay in B-cell homeostasis, fate, and functions.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adoptive Transfer
  • Animals
  • B-Lymphocytes / cytology*
  • B-Lymphocytes / immunology*
  • Blotting, Western
  • Carrier Proteins / genetics
  • Carrier Proteins / immunology*
  • Carrier Proteins / metabolism
  • Cell Differentiation / immunology*
  • Cell Proliferation
  • Cell Survival / immunology
  • Electrophoretic Mobility Shift Assay
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • Homeostasis / immunology*
  • Immunohistochemistry
  • Mice
  • Mice, Inbred C57BL
  • Rapamycin-Insensitive Companion of mTOR Protein
  • Signal Transduction / immunology
  • TOR Serine-Threonine Kinases / genetics
  • TOR Serine-Threonine Kinases / immunology
  • TOR Serine-Threonine Kinases / metabolism

Substances

  • Carrier Proteins
  • Rapamycin-Insensitive Companion of mTOR Protein
  • rictor protein, mouse
  • TOR Serine-Threonine Kinases
  • mTOR protein, mouse