B-cell function in canine X-linked severe combined immunodeficiency

Brian J. Hartnett, Richard L. Somberg, Steven Krakowka, Hans D. Ochs, Harm HogenEsch, Peter F. Moore, Kenneth I. Weinberg, Peter J. Felsburg

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Canine X-linked severe combined immunodeficiency (XSCID) is due to mutations in the common gamma (γc) subunit of the IL-2, IL-4, IL-7, IL-9 and IL-15 receptors and has a similar clinical phenotype to human XSCID. We have previously shown that the block in T-cell development is more profound in XSCID dogs than in genetically engineered γc-deficient mice. In this study we evaluated the B-cell function in XSCID dogs. In contrast to the marked decrease in peripheral B-cells in γc-deficient mice, XSCID dogs have increased proportions and numbers of peripheral B-cells as observed in XSCID boys. Canine XSCID B-cells do not proliferate following stimulation with the T-cell-dependent B-cell mitogen, pokeweed mitogen (PWM); however, they proliferate normally in response to the T-cell-independent B-cell mitogen, formalin-fixed, heat-killed Staphylococcus aureus. Canine XSCID B-cells are capable of producing IgM but are incapable of normal class-switching to IgG antibody production as demonstrated by in vitro stimulation with PWM and immunization with the T-cell-dependent antigen, bacteriophage ΦX174. Similar results have been reported for XSCID boys. Thus, it appears that γc-dependent cytokines have differing roles in human and canine B-cell development than in the mouse making the XSCID dog a valuable model for studying the role of these cytokines in B-cell development and function. Copyright (C) 2000 Elsevier Science B.V.

Original languageEnglish (US)
Pages (from-to)121-134
Number of pages14
JournalVeterinary Immunology and Immunopathology
Volume75
Issue number1-2
DOIs
StatePublished - Jun 30 2000
Externally publishedYes

Fingerprint

X-Linked Combined Immunodeficiency Diseases
severe combined immunodeficiency
B-lymphocytes
Canidae
B-Lymphocytes
dogs
T-lymphocytes
Dogs
T-Lymphocytes
Pokeweed Mitogens
Phytolacca americana
Mitogens
Interleukin-15 Receptors
mice
interleukin-9
cytokines
Interleukin-9
interleukin-7
Immunoglobulin Class Switching
Cytokines

Keywords

  • B-cells
  • Common gamma chain
  • Cytokine receptors
  • Cytokines
  • Dog
  • Immunodeficiency

ASJC Scopus subject areas

  • Animal Science and Zoology
  • Immunology
  • veterinary(all)

Cite this

Hartnett, B. J., Somberg, R. L., Krakowka, S., Ochs, H. D., HogenEsch, H., Moore, P. F., ... Felsburg, P. J. (2000). B-cell function in canine X-linked severe combined immunodeficiency. Veterinary Immunology and Immunopathology, 75(1-2), 121-134. https://doi.org/10.1016/S0165-2427(00)00193-8

B-cell function in canine X-linked severe combined immunodeficiency. / Hartnett, Brian J.; Somberg, Richard L.; Krakowka, Steven; Ochs, Hans D.; HogenEsch, Harm; Moore, Peter F.; Weinberg, Kenneth I.; Felsburg, Peter J.

In: Veterinary Immunology and Immunopathology, Vol. 75, No. 1-2, 30.06.2000, p. 121-134.

Research output: Contribution to journalArticle

Hartnett, BJ, Somberg, RL, Krakowka, S, Ochs, HD, HogenEsch, H, Moore, PF, Weinberg, KI & Felsburg, PJ 2000, 'B-cell function in canine X-linked severe combined immunodeficiency', Veterinary Immunology and Immunopathology, vol. 75, no. 1-2, pp. 121-134. https://doi.org/10.1016/S0165-2427(00)00193-8
Hartnett, Brian J. ; Somberg, Richard L. ; Krakowka, Steven ; Ochs, Hans D. ; HogenEsch, Harm ; Moore, Peter F. ; Weinberg, Kenneth I. ; Felsburg, Peter J. / B-cell function in canine X-linked severe combined immunodeficiency. In: Veterinary Immunology and Immunopathology. 2000 ; Vol. 75, No. 1-2. pp. 121-134.
@article{6bec48af0ded41219cf7db1d67b0f48e,
title = "B-cell function in canine X-linked severe combined immunodeficiency",
abstract = "Canine X-linked severe combined immunodeficiency (XSCID) is due to mutations in the common gamma (γc) subunit of the IL-2, IL-4, IL-7, IL-9 and IL-15 receptors and has a similar clinical phenotype to human XSCID. We have previously shown that the block in T-cell development is more profound in XSCID dogs than in genetically engineered γc-deficient mice. In this study we evaluated the B-cell function in XSCID dogs. In contrast to the marked decrease in peripheral B-cells in γc-deficient mice, XSCID dogs have increased proportions and numbers of peripheral B-cells as observed in XSCID boys. Canine XSCID B-cells do not proliferate following stimulation with the T-cell-dependent B-cell mitogen, pokeweed mitogen (PWM); however, they proliferate normally in response to the T-cell-independent B-cell mitogen, formalin-fixed, heat-killed Staphylococcus aureus. Canine XSCID B-cells are capable of producing IgM but are incapable of normal class-switching to IgG antibody production as demonstrated by in vitro stimulation with PWM and immunization with the T-cell-dependent antigen, bacteriophage ΦX174. Similar results have been reported for XSCID boys. Thus, it appears that γc-dependent cytokines have differing roles in human and canine B-cell development than in the mouse making the XSCID dog a valuable model for studying the role of these cytokines in B-cell development and function. Copyright (C) 2000 Elsevier Science B.V.",
keywords = "B-cells, Common gamma chain, Cytokine receptors, Cytokines, Dog, Immunodeficiency",
author = "Hartnett, {Brian J.} and Somberg, {Richard L.} and Steven Krakowka and Ochs, {Hans D.} and Harm HogenEsch and Moore, {Peter F.} and Weinberg, {Kenneth I.} and Felsburg, {Peter J.}",
year = "2000",
month = "6",
day = "30",
doi = "10.1016/S0165-2427(00)00193-8",
language = "English (US)",
volume = "75",
pages = "121--134",
journal = "Veterinary Immunology and Immunopathology",
issn = "0165-2427",
publisher = "Elsevier",
number = "1-2",

}

TY - JOUR

T1 - B-cell function in canine X-linked severe combined immunodeficiency

AU - Hartnett, Brian J.

AU - Somberg, Richard L.

AU - Krakowka, Steven

AU - Ochs, Hans D.

AU - HogenEsch, Harm

AU - Moore, Peter F.

AU - Weinberg, Kenneth I.

AU - Felsburg, Peter J.

PY - 2000/6/30

Y1 - 2000/6/30

N2 - Canine X-linked severe combined immunodeficiency (XSCID) is due to mutations in the common gamma (γc) subunit of the IL-2, IL-4, IL-7, IL-9 and IL-15 receptors and has a similar clinical phenotype to human XSCID. We have previously shown that the block in T-cell development is more profound in XSCID dogs than in genetically engineered γc-deficient mice. In this study we evaluated the B-cell function in XSCID dogs. In contrast to the marked decrease in peripheral B-cells in γc-deficient mice, XSCID dogs have increased proportions and numbers of peripheral B-cells as observed in XSCID boys. Canine XSCID B-cells do not proliferate following stimulation with the T-cell-dependent B-cell mitogen, pokeweed mitogen (PWM); however, they proliferate normally in response to the T-cell-independent B-cell mitogen, formalin-fixed, heat-killed Staphylococcus aureus. Canine XSCID B-cells are capable of producing IgM but are incapable of normal class-switching to IgG antibody production as demonstrated by in vitro stimulation with PWM and immunization with the T-cell-dependent antigen, bacteriophage ΦX174. Similar results have been reported for XSCID boys. Thus, it appears that γc-dependent cytokines have differing roles in human and canine B-cell development than in the mouse making the XSCID dog a valuable model for studying the role of these cytokines in B-cell development and function. Copyright (C) 2000 Elsevier Science B.V.

AB - Canine X-linked severe combined immunodeficiency (XSCID) is due to mutations in the common gamma (γc) subunit of the IL-2, IL-4, IL-7, IL-9 and IL-15 receptors and has a similar clinical phenotype to human XSCID. We have previously shown that the block in T-cell development is more profound in XSCID dogs than in genetically engineered γc-deficient mice. In this study we evaluated the B-cell function in XSCID dogs. In contrast to the marked decrease in peripheral B-cells in γc-deficient mice, XSCID dogs have increased proportions and numbers of peripheral B-cells as observed in XSCID boys. Canine XSCID B-cells do not proliferate following stimulation with the T-cell-dependent B-cell mitogen, pokeweed mitogen (PWM); however, they proliferate normally in response to the T-cell-independent B-cell mitogen, formalin-fixed, heat-killed Staphylococcus aureus. Canine XSCID B-cells are capable of producing IgM but are incapable of normal class-switching to IgG antibody production as demonstrated by in vitro stimulation with PWM and immunization with the T-cell-dependent antigen, bacteriophage ΦX174. Similar results have been reported for XSCID boys. Thus, it appears that γc-dependent cytokines have differing roles in human and canine B-cell development than in the mouse making the XSCID dog a valuable model for studying the role of these cytokines in B-cell development and function. Copyright (C) 2000 Elsevier Science B.V.

KW - B-cells

KW - Common gamma chain

KW - Cytokine receptors

KW - Cytokines

KW - Dog

KW - Immunodeficiency

UR - http://www.scopus.com/inward/record.url?scp=0034734020&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034734020&partnerID=8YFLogxK

U2 - 10.1016/S0165-2427(00)00193-8

DO - 10.1016/S0165-2427(00)00193-8

M3 - Article

VL - 75

SP - 121

EP - 134

JO - Veterinary Immunology and Immunopathology

JF - Veterinary Immunology and Immunopathology

SN - 0165-2427

IS - 1-2

ER -