Partial restoration of B cell development in Jak‐3^–/– mice achieved by co‐expression of IgH and E_µ‐myc transgenes

Abstract

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 (TCRα^–/–) 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.

B lymphocyte, c‐myc, FACS, Ig, transgenic mice, TCRα‐deficient mice