title: TSC1 Promotes B Cell Maturation but Is Dispensable for Germinal Center Formation.
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.
authors.affiliation: Department of Pediatrics, Duke University Medical Center, Durham, NC, 27710, United States of America; Key Laboratory of Zoonosis Ministry of Education, Institute of Zoonosis, College of Animal Science and Veterinary Medicine, Jilin University, Changchun, 130062, China.
authors.forename: Xinxin
authors.initials: X
authors.lastname: Ci
authors.affiliation: Department of Immunology, Duke University Medical Center, Durham, NC, 27710, United States of America.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Kuraoka
authors.affiliation: Department of Pediatrics, Duke University Medical Center, Durham, NC, 27710, United States of America; Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, China.
authors.forename: Hongxia
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Immunology, Duke University Medical Center, Durham, NC, 27710, United States of America.
authors.forename: Zachary
authors.initials: Z
authors.lastname: Carico
authors.affiliation: Department of Immunology, Duke University Medical Center, Durham, NC, 27710, United States of America.
authors.forename: Kristen
authors.initials: K
authors.lastname: Hopper
authors.affiliation: Department of Pediatrics, Duke University Medical Center, Durham, NC, 27710, United States of America.
authors.forename: Jinwook
authors.initials: J
authors.lastname: Shin
authors.affiliation: Key Laboratory of Zoonosis Ministry of Education, Institute of Zoonosis, College of Animal Science and Veterinary Medicine, Jilin University, Changchun, 130062, China.
authors.forename: Xuming
authors.initials: X
authors.lastname: Deng
authors.affiliation: Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, China.
authors.forename: Yirong
authors.initials: Y
authors.lastname: Qiu
authors.affiliation: Department of Immunology, Duke University Medical Center, Durham, NC, 27710, United States of America.
authors.forename: Shyam
authors.initials: S
authors.lastname: Unniraman
authors.affiliation: Department of Immunology, Duke University Medical Center, Durham, NC, 27710, United States of America.
authors.forename: Garnett
authors.initials: G
authors.lastname: Kelsoe
authors.affiliation: Department of Pediatrics, Duke University Medical Center, Durham, NC, 27710, United States of America; Department of Immunology, Duke University Medical Center, Durham, NC, 27710, United States of America.
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Zhong
mesh_terms: D056704:Adaptive Immunity / Q000276:immunology; D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D018858:Germinal Center / Q000276:immunology / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000276:immunology; D000076222:Mechanistic Target of Rapamycin Complex 1; D000076225:Mechanistic Target of Rapamycin Complex 2; D051379:Mice; D018345:Mice, Knockout; D046912:Multiprotein Complexes / Q000378:metabolism; D010581:Peyer's Patches / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*; D013154:Spleen / Q000276:immunology / Q000378:metabolism*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D000077004:Tuberous Sclerosis Complex 1 Protein; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D046912:Multiprotein Complexes; C000624651:Tsc1 protein, mouse; D000077004:Tuberous Sclerosis Complex 1 Protein; D025521:Tumor Suppressor Proteins; D000076222:Mechanistic Target of Rapamycin Complex 1; D000076225:Mechanistic Target of Rapamycin Complex 2; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases