Partial restoration of B cell development in Jak-3(-/-) mice achieved by co-expression of IgH and E(mu)-myc transgenes.
Jak-3 is a non-receptor tyrosine kinase that plays an important role in coordinating signals received through a wide range of cytokine receptors, including the IL-7 receptor (IL-7R). Jak-3-deficient mice have a profound block in B cell development at the pro-to-pre-B cell transition and have very few peripheral B cells. This block has been postulated to reflect the inability of Jak-3(-/-) pro-B cells to respond to IL-7. Here we demonstrate that B cell development can be partially restored in Jak-3-deficient mice when they are bred to mice carrying both a rearranged Ig heavy chain (IgH/Igmu) transgene and a c-myc transgene expressed in the B cell lineage. Jak-3(-/-) mice expressing both of these transgenes exhibit significant increases in the number of B cells in the bone marrow and, to a lesser extent, in the spleen. However, very few rescued B cells were detectable in mice greater than 4 months of age. To determine whether resident hyperactivated Jak-3(-/-) peripheral T cells are responsible for the elimination of the rescued B cells in older mice, we bred IgH transgenic (Igmu Tg)/myc Tg/Jak-3(-/-) mice to T cell-deficient (TCRalpha(-/-)) mice. Data from these experiments suggest that the paucity of B cells in older Jak-3(-/-) mice is largely attributable to the lack of Jak-3 in the B cells themselves. Thus, Jak-3 seems to play several important roles in B cells: during development, to enable cell division, Ig gene rearrangement and cell differentiation, and in mature cells, to promote B cell survival in the periphery.
Dillon
Stacey R
SR
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Schlissel
Mark S
MS
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000201:enzymology / Q000276:immunology*; D001483:Base Sequence; D002454:Cell Differentiation; D002470:Cell Survival; D018076:DNA, Complementary / Q000235:genetics; D015870:Gene Expression; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D019673:Genes, T-Cell Receptor alpha; D016259:Genes, myc; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007148:Immunoglobulin mu-Chains / Q000235:genetics; D053616:Janus Kinase 3; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011505:Protein-Tyrosine Kinases / Q000172:deficiency* / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology
D018076:DNA, Complementary; D007143:Immunoglobulin Heavy Chains; D007148:Immunoglobulin mu-Chains; D011505:Protein-Tyrosine Kinases; C507935:Jak3 protein, mouse; D053616:Janus Kinase 3