International Immunology, Vol. 14, No. 8, pp. 893-904,
August 2002
© 2002 Japanese Society for Immunology
Partial restoration of B cell development in Jak-3–/– mice achieved by co-expression of IgH and Eµ-myc transgenes
1 Departments of Medicine, Molecular Biology and Genetics, and Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA 2 Present address: ZymoGenetics, Seattle, WA 98102, USA 3 Present address: Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720-3200, USA.
Correspondence to: M. S. Schlissel, Department of Molecular and Cell Biology, 439 LSA, University of California, Berkeley, CA 94720-3200, USA. E-mail: mss{at}uclink4.berkeley.edu
Transmitting editor: P. Kincade
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/Igµ) 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 (Igµ Tg)/myc Tg/Jak-3–/– mice to T cell-deficient (TCR
–/–) 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.
Keywords: B lymphocyte, c-myc, FACS, Ig, transgenic mice, TCR-deficient mice
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