Agammaglobulinemia and absent B lineage cells in a patient lacking the p85α subunit of PI3K

Mary Ellen Conley, A. Kerry Dobbs, Anita M. Quintana, Amma Bosompem, Yong Dong Wang, Elaine Coustan-Smith, Amber Smith, Elena E. Perez, Peter J. Murray

Research output: Contribution to journalArticle

117 Citations (Scopus)

Abstract

Whole exome sequencing was used to determine the causative gene in patients with B cell defects of unknown etiology. A homozygous premature stop codon in exon 6 of PIK3R1 was identified in a young woman with colitis and absent B cells. The mutation results in the absence of p85α but normal expression of the p50α and p55α regulatory subunits of PI3K. Bone marrow aspirates from the patient showed <0.1% CD19 + B cells with normal percentages of TdT + VpreB + CD19 - B cell precursors. This developmental block is earlier than that seen in patients with defects in the B cell receptor signaling pathway or in a strain of engineered mice with a similar defect in p85α. The number and function of the patient's T cells were normal. However, Western blot showed markedly decreased p110δ, as well as absent p85α, in patient T cells, neutrophils, and dendritic cells. The patient had normal growth and development and normal fasting glucose and insulin. Mice with p85α deficiency have insulin hypersensitivity, defective platelet function, and abnormal mast cell development. In contrast, the absence of p85α in the patient results in an early and severe defect in B cell development but minimal findings in other organ systems.

Original languageEnglish (US)
Pages (from-to)463-470
Number of pages8
JournalJournal of Experimental Medicine
Volume209
Issue number3
DOIs
StatePublished - Mar 12 2012

Fingerprint

Agammaglobulinemia
Phosphatidylinositol 3-Kinases
B-Lymphocytes
Insulin
Exome
T-Lymphocytes
B-Lymphoid Precursor Cells
Nonsense Codon
Colitis
Growth and Development
Mast Cells
Dendritic Cells
Exons
Fasting
Hypersensitivity
Neutrophils
Blood Platelets
Bone Marrow
Western Blotting
Glucose

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Conley, M. E., Dobbs, A. K., Quintana, A. M., Bosompem, A., Wang, Y. D., Coustan-Smith, E., ... Murray, P. J. (2012). Agammaglobulinemia and absent B lineage cells in a patient lacking the p85α subunit of PI3K. Journal of Experimental Medicine, 209(3), 463-470. https://doi.org/10.1084/jem.20112533

Agammaglobulinemia and absent B lineage cells in a patient lacking the p85α subunit of PI3K. / Conley, Mary Ellen; Dobbs, A. Kerry; Quintana, Anita M.; Bosompem, Amma; Wang, Yong Dong; Coustan-Smith, Elaine; Smith, Amber; Perez, Elena E.; Murray, Peter J.

In: Journal of Experimental Medicine, Vol. 209, No. 3, 12.03.2012, p. 463-470.

Research output: Contribution to journalArticle

Conley, ME, Dobbs, AK, Quintana, AM, Bosompem, A, Wang, YD, Coustan-Smith, E, Smith, A, Perez, EE & Murray, PJ 2012, 'Agammaglobulinemia and absent B lineage cells in a patient lacking the p85α subunit of PI3K', Journal of Experimental Medicine, vol. 209, no. 3, pp. 463-470. https://doi.org/10.1084/jem.20112533
Conley ME, Dobbs AK, Quintana AM, Bosompem A, Wang YD, Coustan-Smith E et al. Agammaglobulinemia and absent B lineage cells in a patient lacking the p85α subunit of PI3K. Journal of Experimental Medicine. 2012 Mar 12;209(3):463-470. https://doi.org/10.1084/jem.20112533
Conley, Mary Ellen ; Dobbs, A. Kerry ; Quintana, Anita M. ; Bosompem, Amma ; Wang, Yong Dong ; Coustan-Smith, Elaine ; Smith, Amber ; Perez, Elena E. ; Murray, Peter J. / Agammaglobulinemia and absent B lineage cells in a patient lacking the p85α subunit of PI3K. In: Journal of Experimental Medicine. 2012 ; Vol. 209, No. 3. pp. 463-470.
@article{5ade6e414b944e5ea2aaf4d9b26a8b58,
title = "Agammaglobulinemia and absent B lineage cells in a patient lacking the p85α subunit of PI3K",
abstract = "Whole exome sequencing was used to determine the causative gene in patients with B cell defects of unknown etiology. A homozygous premature stop codon in exon 6 of PIK3R1 was identified in a young woman with colitis and absent B cells. The mutation results in the absence of p85α but normal expression of the p50α and p55α regulatory subunits of PI3K. Bone marrow aspirates from the patient showed <0.1{\%} CD19 + B cells with normal percentages of TdT + VpreB + CD19 - B cell precursors. This developmental block is earlier than that seen in patients with defects in the B cell receptor signaling pathway or in a strain of engineered mice with a similar defect in p85α. The number and function of the patient's T cells were normal. However, Western blot showed markedly decreased p110δ, as well as absent p85α, in patient T cells, neutrophils, and dendritic cells. The patient had normal growth and development and normal fasting glucose and insulin. Mice with p85α deficiency have insulin hypersensitivity, defective platelet function, and abnormal mast cell development. In contrast, the absence of p85α in the patient results in an early and severe defect in B cell development but minimal findings in other organ systems.",
author = "Conley, {Mary Ellen} and Dobbs, {A. Kerry} and Quintana, {Anita M.} and Amma Bosompem and Wang, {Yong Dong} and Elaine Coustan-Smith and Amber Smith and Perez, {Elena E.} and Murray, {Peter J.}",
year = "2012",
month = "3",
day = "12",
doi = "10.1084/jem.20112533",
language = "English (US)",
volume = "209",
pages = "463--470",
journal = "Journal of Experimental Medicine",
issn = "0022-1007",
publisher = "Rockefeller University Press",
number = "3",

}

TY - JOUR

T1 - Agammaglobulinemia and absent B lineage cells in a patient lacking the p85α subunit of PI3K

AU - Conley, Mary Ellen

AU - Dobbs, A. Kerry

AU - Quintana, Anita M.

AU - Bosompem, Amma

AU - Wang, Yong Dong

AU - Coustan-Smith, Elaine

AU - Smith, Amber

AU - Perez, Elena E.

AU - Murray, Peter J.

PY - 2012/3/12

Y1 - 2012/3/12

N2 - Whole exome sequencing was used to determine the causative gene in patients with B cell defects of unknown etiology. A homozygous premature stop codon in exon 6 of PIK3R1 was identified in a young woman with colitis and absent B cells. The mutation results in the absence of p85α but normal expression of the p50α and p55α regulatory subunits of PI3K. Bone marrow aspirates from the patient showed <0.1% CD19 + B cells with normal percentages of TdT + VpreB + CD19 - B cell precursors. This developmental block is earlier than that seen in patients with defects in the B cell receptor signaling pathway or in a strain of engineered mice with a similar defect in p85α. The number and function of the patient's T cells were normal. However, Western blot showed markedly decreased p110δ, as well as absent p85α, in patient T cells, neutrophils, and dendritic cells. The patient had normal growth and development and normal fasting glucose and insulin. Mice with p85α deficiency have insulin hypersensitivity, defective platelet function, and abnormal mast cell development. In contrast, the absence of p85α in the patient results in an early and severe defect in B cell development but minimal findings in other organ systems.

AB - Whole exome sequencing was used to determine the causative gene in patients with B cell defects of unknown etiology. A homozygous premature stop codon in exon 6 of PIK3R1 was identified in a young woman with colitis and absent B cells. The mutation results in the absence of p85α but normal expression of the p50α and p55α regulatory subunits of PI3K. Bone marrow aspirates from the patient showed <0.1% CD19 + B cells with normal percentages of TdT + VpreB + CD19 - B cell precursors. This developmental block is earlier than that seen in patients with defects in the B cell receptor signaling pathway or in a strain of engineered mice with a similar defect in p85α. The number and function of the patient's T cells were normal. However, Western blot showed markedly decreased p110δ, as well as absent p85α, in patient T cells, neutrophils, and dendritic cells. The patient had normal growth and development and normal fasting glucose and insulin. Mice with p85α deficiency have insulin hypersensitivity, defective platelet function, and abnormal mast cell development. In contrast, the absence of p85α in the patient results in an early and severe defect in B cell development but minimal findings in other organ systems.

UR - http://www.scopus.com/inward/record.url?scp=84860359332&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84860359332&partnerID=8YFLogxK

U2 - 10.1084/jem.20112533

DO - 10.1084/jem.20112533

M3 - Article

VL - 209

SP - 463

EP - 470

JO - Journal of Experimental Medicine

JF - Journal of Experimental Medicine

SN - 0022-1007

IS - 3

ER -