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 language | English (US) |
|---|---|
| Pages (from-to) | 121-134 |
| Number of pages | 14 |
| Journal | Veterinary Immunology and Immunopathology |
| Volume | 75 |
| Issue number | 1-2 |
| DOIs | |
| State | Published - Jun 30 2000 |
Fingerprint
Keywords
- B-cells
- Common gamma chain
- Cytokine receptors
- Cytokines
- Dog
- Immunodeficiency
ASJC Scopus subject areas
- Immunology
- veterinary(all)
Cite this
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 journal › Article
}
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
C2 - 10889304
AN - SCOPUS:0034734020
VL - 75
SP - 121
EP - 134
JO - Veterinary Immunology and Immunopathology
JF - Veterinary Immunology and Immunopathology
SN - 0165-2427
IS - 1-2
ER -