TY - JOUR
T1 - Lymphocytes lacking IκB-α develop normally, but have selective defects in proliferation and function
AU - Chen, C. L.
AU - Singh, N.
AU - Yull, F. E.
AU - Strayhorn, D.
AU - Van Kaer, L.
AU - Kerr, L. D.
PY - 2000/11/15
Y1 - 2000/11/15
N2 - NF-κB has been implicated in the development, activation, and function of B and T lymphocytes. We have evaluated the in vivo effects of deletion of IκB-α, a major inhibitor of NF-κB, on lymphocyte development, proliferation, and function. To elucidate the long term role of IκB-α in lymphocytes, fetal liver cells of 14.5-day-old IκB-α(-/-) or wild-type embryos were transplanted into irradiated recombinase-activating gene-2-deficient mice. Within 4 wk, the IκB-α(-/-) fetal liver cells reconstitute mature B and T cell populations in the recipients comparable to those produced by wild-type fetal liver cells. However, the proliferative responses of IκB-α(-/-) B cells are enhanced, whereas those of IκB-α(-/-) T cells are reduced. The levels of IgG1, IgG2a, IgA, and IgE produced by IκB-α(-/-) B cells are elevated relative to those produced by IκB-α(+/+) or IκB-α(+/-). Moreover, the specific immune responses to OVA and the generation of germinal centers are impaired in recipients of IκB-α(-/-) fetal liver cells. These results indicate that IκB-α plays a vital role in signal transduction pathways regulating lymphocyte proliferation and also in the production of specific Ig isotypes.
AB - NF-κB has been implicated in the development, activation, and function of B and T lymphocytes. We have evaluated the in vivo effects of deletion of IκB-α, a major inhibitor of NF-κB, on lymphocyte development, proliferation, and function. To elucidate the long term role of IκB-α in lymphocytes, fetal liver cells of 14.5-day-old IκB-α(-/-) or wild-type embryos were transplanted into irradiated recombinase-activating gene-2-deficient mice. Within 4 wk, the IκB-α(-/-) fetal liver cells reconstitute mature B and T cell populations in the recipients comparable to those produced by wild-type fetal liver cells. However, the proliferative responses of IκB-α(-/-) B cells are enhanced, whereas those of IκB-α(-/-) T cells are reduced. The levels of IgG1, IgG2a, IgA, and IgE produced by IκB-α(-/-) B cells are elevated relative to those produced by IκB-α(+/+) or IκB-α(+/-). Moreover, the specific immune responses to OVA and the generation of germinal centers are impaired in recipients of IκB-α(-/-) fetal liver cells. These results indicate that IκB-α plays a vital role in signal transduction pathways regulating lymphocyte proliferation and also in the production of specific Ig isotypes.
UR - http://www.scopus.com/inward/record.url?scp=0034670001&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0034670001&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.165.10.5418
DO - 10.4049/jimmunol.165.10.5418
M3 - Article
C2 - 11067893
AN - SCOPUS:0034670001
SN - 0022-1767
VL - 165
SP - 5418
EP - 5427
JO - Journal of Immunology
JF - Journal of Immunology
IS - 10
ER -